CN116942686A - Application of salidroside in preparing medicine for treating heart ion channel diseases - Google Patents

Application of salidroside in preparing medicine for treating heart ion channel diseases Download PDF

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CN116942686A
CN116942686A CN202311202796.4A CN202311202796A CN116942686A CN 116942686 A CN116942686 A CN 116942686A CN 202311202796 A CN202311202796 A CN 202311202796A CN 116942686 A CN116942686 A CN 116942686A
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salidroside
channel
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王小博
孟宪丽
张艺
张雅婷
侯娅
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Chengdu University of Traditional Chinese Medicine
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Abstract

The invention belongs to the field of biological medicine, and in particular provides application of salidroside in preparing medicines for treating heart ion channel diseases. The application of the salidroside in preparing the medicine for preventing and/or treating the heart ion channel diseases is proved by a cell test: salidroside for normal myocardial cell K v Total channel and K v 2.1 channel currents are all inhibited and have a K-effect v The effect of the total channel current is concentration dependent but K in the anoxic state v Total channel and K v 2.1 myocardial cells in which channel currents are suppressed have an ameliorating effect and exhibit concentration-dependent resistance to K v Total channel and K v The 2.1 channel current can be restored to normal level. Use of salidroside for preventing and/or treating myocardial cell K + Abnormal ion channel causesHas good effect on heart ion channel diseases, in particular to long QT syndrome, and has practical clinical popularization and application values.

Description

Application of salidroside in preparing medicine for treating heart ion channel diseases
Technical Field
The invention belongs to the field of biological medicine, and in particular relates to application of salidroside in preparing medicines for treating heart ion channel diseases.
Background
Cardiac ion channel diseases refer to a group of genetic diseases in which the mutation of genes encoding the main ion channel subunits of myocardial cells causes ion channel dysfunction, and most of the genetic diseases have special electrocardiographic manifestations. The ion channel of myocardial cell membrane closely related to electrocardio has Na + 、K + 、Ca + 、Cl - A channel, wherein K + The channel structure is simple, the variety is the most, is the basic unit of channel structure. K (K) + Kv (voltage-gated potassium channel) in the channel is repolarizing current that restores action potential to rest state, and the QT interval is prolonged by reduced activity.
Long QT syndrome is a common clinical type of heart ion channel disease characterized by prolongation of ventricular repolarization (prolongation of QT interval), susceptibility to torsades de pointes, fibrillation and sudden cardiac death, which are classified into two major categories, i.e., congenital inheritance and acquired, depending on the presence or absence of secondary factors. At present, the medicine treatment mainly uses beta receptor antagonist, but the medicine has obvious side effect, and adverse reactions of bradycardia and some influence on life quality can occur in the use process, and the medicine withdrawal syndrome can be caused by sudden stopping of medicine at the time of higher dose treatment.
Rhodiola rosea glycoside with molecular formula of C 14 H 20 O 7 Is one of main active monomer components of rhodiola rosea, has the effects of resisting atherosclerosis, dilating coronary artery, reducing peripheral circulation resistance, increasing cardiac output and the like, and has important effects on cardiovascular and cerebrovascular diseases, nervous system diseases, metabolic syndrome, cancer and the like. Researches show that the salidroside can improve protein expression of myocardial cells in the hypoxia injury state and reduce the occurrence of hypoxia myocardial cells such as hypoxia myocardial cell autophagy and the likeThe protection function is played. However, no method for treating heart ion channel diseases, especially K, by salidroside is known at present + Application research of long Q-T interval syndrome, which is a heart ion channel disease caused by ion channel abnormality.
Disclosure of Invention
In order to solve the problems, the invention provides the application of salidroside in preparing medicines for preventing and/or treating heart ion channel diseases.
Further, the cardiac ion channel disease includes long Q-T interval syndrome, short Q-T interval syndrome, brugada syndrome, or catecholamine sensitive polymorphic ventricular tachycardia.
Further, the cardiac ion channel disorder is long Q-T interval syndrome.
Further, the medicine is used for inhibiting normal myocardial cell K v Drug of total channel current.
Further, the medicine is capable of inhibiting normal myocardial cell K v 2.1 channel current drug.
Further, the medicament enhances hypoxic cardiomyocyte K v Drug of total channel current.
Further, the medicament enhances hypoxic cardiomyocyte K v 2.1 channel current drug.
Further, the medicine is a preparation prepared by taking salidroside as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Still further, the formulation is an oral formulation.
Further, the oral preparation is a solution, a granule, a pill, a paste, a tablet or a capsule.
The invention has the beneficial effects that:
the application of the salidroside in preparing the medicine for treating the heart ion channel diseases is proved by a cell test: salidroside for normal myocardial cell K v Total channel and K v 2.1 channel currents are all inhibited and have a K-effect v The effect of the total channel current is concentration dependent but K in the anoxic state v Total channel and K v 2.1 myocardial cells in which channel currents are suppressed have an ameliorating effect and exhibit concentration-dependent resistance to K v Total channel and K v The 2.1 channel current can be restored to normal level. Use of salidroside for preventing and/or treating myocardial cell K + The heart ion channel diseases caused by the abnormality of the ion channel, in particular to the long QT syndrome, have good effects and have practical clinical popularization and application values.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
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FIG. 1 is a graph showing the effect of salidroside on electrocardiogram of SD rat long QT syndrome caused by cisapride. A-F are schematic electrocardiographic recordings of different time points of a blank group (Control), a model group (Cis.) and a salidroside group (cis.+Sal) salidroside.
FIG. 2 shows the effect of salidroside on the prevention and treatment of SD rat long QT syndrome caused by cisapride. A-L are the effects on SD rat heart rate, RR interval, PR interval, QRS interval, QT interval, QTc interval, JT interval, end-of-peak interval, P wave, R wave, T wave, S wave amplitude index after administration, respectively. * P＜0.05， * * P＜0.01， * * * P＜0.001， * * * * P＜0.0001；n=5。
FIG. 3 is a graph showing the effect of salidroside on H9c2 cell viability. Compared to the blank groupP<0.05，**P<0.01; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05， ## P<0.05；n=4。
FIG. 4 shows salidroside versus H9c2 cell K v The effect of the total channel current. A is a schematic representation of cell status; b is the Kv total channel current stimulation program; C. d is an I-V curve of salidroside to the Kv total channel current of H9c2 cells in blank and modeling states respectively; n=5.
FIG. 5 is a 1.5 mM 4-AP vs. H9c2 cell K v Graph of the effect of total current density. a-B represent representative current curves recorded in the blank and 4-AP groups, respectively, C is their I-V curves, compared to the blank groupP<0.05；n=5。
FIG. 6 is a graph showing the effect of 5. Mu.M salidroside on H9c2 cells v Graph of the effect of total current density. A-C represent representative current curves recorded in the blank, 4-AP, 5 μM salidroside, and D are their I-V curves, respectively, compared to the blankP<0.05；n=5。
FIG. 7 is a graph showing the effect of 10. Mu.M salidroside on H9c2 cells v Graph of the effect of total current density. A-C represent representative current curves recorded in the blank, 4-AP, 10 μM salidroside, and D are their I-V curves, respectively, compared to the blankP<0.05；n=5。
FIG. 8 is a graph showing the effect of 20. Mu.M salidroside on H9c2 cells v Graph of the effect of total current density. A-C represent representative current curves recorded in the blank, 4-AP, 20. Mu.M salidroside, and D are their I-V curves, respectively, compared to the blankP<0.05；n=5。
FIG. 9 is a graph of 40. Mu.M salidroside versus H9c2 cells v Graph of the effect of total current density. A-C represent representative current curves recorded in the blank, 4-AP, 40. Mu.M salidroside, and D are their I-V curves, respectively, compared to the blankP<0.05；n=5。
FIG. 10 is a graph of 80. Mu.M salidroside versus H9c2 cells v Graph of the effect of total current density. A-C represent representative current curves recorded in the blank, 4-AP, and 80. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 11 is 300. Mu.M CoCl 2 K for H9c2 cells v Operation of total current densityThe result graph is used. A-B respectively represent blank groups, coCl 2 Representative current curves recorded by the group, C being their I-V curves, compared to the blank groupP<0.05；n=5。
FIG. 12 shows a graph of 5. Mu.M salidroside versus CoCl 2 Modeling K of H9c2 cells v Graph of the effect of total current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 5 μm salidroside group, D is their I-V curve; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 13 is a 10. Mu.M salidroside vs. CoCl 2 Modeling K of H9c2 cells v Graph of the effect of total current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 10 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 14 is 20. Mu.M salidroside vs. CoCl 2 Modeling K of H9c2 cells v Graph of the effect of total current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 20 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 15 is a 40. Mu.M salidroside versus CoCl 2 Modeling K of H9c2 cells v Graph of the effect of total current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 40 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 16 is 80. Mu.M salidroside vs. CoCl 2 Modeling K of H9c2 cells v Graph of the effect of total current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 80 μM salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 17 shows salidroside versus H9c2 cell K v 2.1 action results of channel current density. A is K v 2.1 channel current stimulation procedure; B. c respectively represents emptyUnder the molding state of rhizoma bletillae, the salidroside has an I-V curve for H9c2 cell Kv2.1 channel current; n=5.
FIG. 18 is a graph of 50 mM citalopram versus H9c2 cells v 2.1 action results of current density. a-B represent representative current curves recorded in the blank and citalopram groups, respectively, C is their I-V curves, compared to the blank groupP<0.05；n=5。
FIG. 19 is a graph showing the effect of 5. Mu.M salidroside on H9c2 cells v 2.1 action results of current density. A-C represent representative current curves recorded in the blank, citalopram, and 5. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 20 is a graph of 10. Mu.M salidroside versus H9c2 cells K v 2.1 action results of current density. A-C represent representative current curves recorded in the blank, citalopram, and 10. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 21 is a 20. Mu.M salidroside versus H9c2 cell K v 2.1 action results of current density. A-C represent representative current curves recorded in the blank, citalopram, and 20. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 22 is a graph of 40. Mu.M salidroside versus H9c2 cells v 2.1 action results of current density. A-C represent representative current curves recorded in the blank, citalopram, and 40. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 23 is a graph of 80. Mu.M salidroside versus H9c2 cells v 2.1 action results of current density. A-C represent representative current curves recorded in the blank, citalopram, and 80. Mu.M salidroside groups, respectively, D is their I-V curves, compared to the blankP<0.05；n=5。
FIG. 24 is 300. Mu.M CoCl 2 K for H9c2 cells v 2.1 action results of current density. A-B respectively represent blank groups, coCl 2 Representative current curves recorded by the group, C being their I-V curves, compared to the blank groupP<0.05；n=5。
FIG. 25 shows a graph of 5. Mu.M salidroside versus CoCl 2 Modeling K of H9c2 cells v 2.1 action results of current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 5 μm salidroside group, D is their I-V curve; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 26 is a graph of 10. Mu.M salidroside versus CoCl 2 Modeling K of H9c2 cells v 2.1 action results of current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 10 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 27 is 20. Mu.M salidroside vs. CoCl 2 Modeling K of H9c2 cells v 2.1 action results of current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 20 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 28 is a 40. Mu.M salidroside versus CoCl 2 Modeling K of H9c2 cells v 2.1 action results of current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 40 μm salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
FIG. 29 is 80. Mu.M salidroside vs. CoCl 2 Modeling K of H9c2 cells v 2.1 action results of current density. A-C respectively represent blank groups, coCl 2 Representative current curves recorded for the group, 80 μM salidroside group, D being their I-V curves; compared with the molding assembly, the molding assembly has the advantages that, # P<0.05；n=5。
Detailed Description
EXAMPLE 1 Studies of salidroside on cardiac ion channel disease
1. SD rat long QT syndrome caused by salidroside prevention and treatment medicine
(1) Experimental method
Healthy male SD rats were selected with a body mass of 280+ -20 g, 10 animals were randomly divided into 5 model groups and 5 animals were dosed. After pentobarbital sodium is injected into abdominal cavity to anesthetize rat, 3 output electrodes of limb leads are sequentially penetrated into the inner sides of one side upper limb and two side lower limbs of the rat by crocodile clip switching needle electrodes, a PowerLab 8/35 system ECG module is adopted to record electrocardiographic data, and after the electrocardiographic data record is stable, cisapride (abbreviated as cis, 10 mg/kg, K) is respectively injected into jugular vein of the model group rat + Channel inhibitors, which can cause the occurrence of long QT syndrome), jugular vein injection cis.10 mg/kg + salidroside 10 mg/kg in rats of the administration group, continuous recording of electrocardiogram 1 h after injection in rats of the two groups, and observation of the effect of salidroside on the electrocardiogram of SD rats. Drawing analysis is carried out on the observed results by adopting Graphpad Prism 9 software, all analysis results are expressed by mean+/-SE, single factor analysis of variance is carried out on experimental data,P<0.05 As a criterion for the difference in significance.
(2) Experimental results: as shown in fig. 1 and 2, the heart rate was significantly reduced and QT interval was prolonged after 10 mg/kg cis.30 min of jugular injection into SD rats; PR interval is obviously shortened, QRS interval, QT interval, QTc interval, JT interval and wave crest interval are prolonged, and amplitudes of P wave, R wave and T wave are increased after administration of 1 h; and when 10 mg/kg cis and 10 mg/kg salidroside are simultaneously administered for 30 min, PR interval, QRS interval, QT interval, QTc interval, JT interval, and peak end interval and amplitudes of P wave, R wave and T wave can be recovered to be close to normal level; besides, the administration of salidroside 1 h can also reduce heart rate and prolong RR intervalP＜0.05）。
Experimental results show that after salidroside is given to a long QT syndrome model, PR interval, QRS interval, QT interval, QTc interval, JT interval, wave crest end interval and amplitudes of P wave, R wave and T wave can be restored to be close to normal levels, so that the salidroside can effectively treat Q-T interval syndromes.
2. Salidroside affects the cell viability of H9c2 cells
(1) Experimental method
H9c2 cells were fused to 80% for passaging,sucking off the culture medium in the dish, washing twice with PBS, adding 1.5 ml concentration 0.05% pancreatin solution for digestion, observing cell retraction and rounding under microscope, adding 3 ml complete culture medium to stop digestion, gently blowing off the cells from the bottom of the dish, and making into cell heavy suspension with density of 5×10 4 Single cell suspensions per ml were inoculated into 96-well plates at 100. Mu.l per well, and a blank set, coCl, was set 2 300. Mu M anoxic group, anoxic+rhodioside concentration gradient group (5, 10, 20, 40, 80, unit: mu M), 7 groups, 4 holes in each group, after cell inoculation 12 h, the culture supernatant was aspirated, and the anoxic group, anoxic+rhodioside concentration gradient group was added with COCl 2 COCl 2 Complete culture medium with different concentrations of +rhodiola rosea is placed in an incubator for 24 and h. Adding fresh complete medium into blank group, placing into CO 2 The incubator continues to incubate 24 h. Cell viability was measured for each group using the CCK-8 method. Drawing analysis is carried out on the observed results by adopting Graphpad Prism 9 software, all analysis results are expressed by mean+/-SE, single factor analysis of variance is carried out on experimental data,P<0.05 As a criterion for the difference in significance.
(2) Experimental results: as shown in FIG. 3, the concentrations of 10-80 mu M of salidroside significantly improve the cell viability of hypoxic HT22 cells, and the difference of the OD value change of 10-80 mu M of salidroside is statistically significant (P < 0.01) compared with the hypoxia group.
3. Salidroside affects H9c2 cell K v Total channel current
(1) Solution preparation
(1) Normal medium of H9c2 cells containing 10% heat-inactivated FBS and 1% penicillin-streptomycin was prepared.
(2) Preparation of 4-aminopyridine (4-AP, K) v Channel inhibitors): 141.165 mg of 4-AP was added to 100. Mu.L of DMSO solution.
(3) 80 mM salidroside mother liquor was prepared, and 12.0122 mg salidroside was added to 500. Mu.L DMSO solution.
(4) Preparing an electrode inner liquid: 0.4100 g KCl (130.0 mM), 0.0120 g MgCl 2 （1.2 mM），0.1270 g Na 2 ATP （5. 5 mM), 0.1190g HEPES (10.0 mM), 0.1900 g EGTA (10.0 mM) was added to 50mL pure water, the pH was adjusted to 7.2 with 1M KOH, and the mixture was filtered and packaged and stored at-20 ℃.
(5) Preparing extracellular fluid: 0.0185 g KCl (5.0 mM), 0.3945 g NaCl (135.0 mM), 0.0203 g MgCl 2 ·6H 2 O (2.0 mM), 0.0595 g HEPES (5 mM), 0.0990 gD-glucose (10.0 mM) was added to 50mL pure water, pH was adjusted to 7.4 with 1M NaOH, and the mixture was filtered and stored to 4 ℃.
(2) Cell culture: h9c2 cells were grown to 80% in normal cell culture medium, digested with trypsin for 30 s, and then added to petri dishes with small glass plates, and treated with normal medium (Control blank) and drug-containing medium (salidroside group: 5, 10, 20, 40, 80. Mu.M salidroside Sal, model group: 300. Mu.M CoCl) without drug solution, respectively 2 Model + salidroside group: 300. mu M CoCl 2 +5, 10, 20, 40, 80. Mu.M salidroside Sal) was cultured for 24 h.
(3) Drawing a glass electrode: first, the "Ramp" value of the glass capillary is detected, and an electrode drawing program is set based on the result of the measured "Ramp" value. And fixing the glass capillary on an electrode drawing instrument, ensuring that the middle part of the capillary is not touched to prevent the tip of the electrode from being polluted, and drawing the electrode by using a set program.
(4) Whole-cell patch clamp technical detection
(1) The glass sheets respectively attached with the cells of each group are transferred into a bath tank of a whole cell patch clamp system, and 1 ml electrode external liquid is added into the bath tank, wherein 4-A mother liquid is also added into the glass sheets partially attached with the cells of the blank group, so that the concentration is 1.5 mM after the glass sheets are diluted.
(2) 30% -60% of the intra-electrode liquid was added to the glass electrode and fixed on the electrode holder, and positive pressure was applied using a 1 mL syringe.
(3) The micromanipulator was used to move the electrode to the point where the electrode tip was immersed in extracellular fluid, square waves were observed on the "back" page of the recording software Clampex with an electrode resistance of 2-6M Ω, and clicking on "Pipette" on the MultiClamp 700B software compensated the baseline to 0pA.
(4) After the electrodes were contacted with the cells, a 1/3 to 1/2 drop in square wave on the clamtex software was observed, the positive pressure was removed, a negative pressure of 0.05 mL to 0.1 mL was rapidly applied using a 1 mL syringe, and then a jump was made to "Patch" page view "the membrane test" approaching 0pA and 1G Ω, with "CpFast" and "Cp Slow" compensation using multicamp 700B software.
(5) After the resistance is stabilized to be more than 1G omega, a short negative pressure pulse is applied to break the membrane adsorbed by the electrode, then the membrane jumps to a 'Cell' interface, after the Cell state is stabilized, multi clamp 700B software is adopted to compensate 'white Cell', recording is started, and the recorded stimulation program is as follows: the clamping voltage of the cells was-60 mV, the cell membrane voltage was clamped at-60 mV, and each 10 mV rise was stimulated in a 150 ms Ramp mode from-40 mV up to +60mV with 220 ms current intervals.
(5) Electrophysiological experiments raw data were recorded and collected with clamex software, preliminary analysis was performed on the raw data using Clamfit software, and then data were imported into Origin 7.5 software for statistical analysis and mapping. The current density calculation formula is: i pA/pF =I pA C, wherein I pA/pF Indicating current density, I pA Representing the detected current, C representing the film capacitance; the maximum inhibition rate calculation formula for the current is as follows: (1-I) pA/pF administration group /I pA/pF blank group ) ✕ 100% and the maximum effective rate of the current is calculated as (I) pA/pF administration group /I pA/pF model group -1) ✕%, all inhibition and effective data were calculated using the current densities recorded at a stimulus voltage of +60 mV. All analysis results are expressed in mean+ -SE, non-parametric tests were performed on experimental data,P<0.05 As a criterion for the difference in significance.
(6) Experimental results: the decrease in current density of H9c2 cells under the action of 4-AP, recorded from FIG. 3, indicates that K can be recorded by the whole cell patch clamp technique v Variation of total channel current (fig. 4). The results according to fig. 4-16: salidroside is empty to H9c2 cell K v The total channel current has concentration-dependent resistance inhibition effect, and its effect is not greatly different at 10-80 μm, and the stimulus voltage isAt +60mV, the maximum inhibition rate of salidroside is 61.07%; while salidroside pair CoCl 2 H9c2 cell K after molding v The total channel current has an increasing effect, which is most remarkable at 20-40. Mu.M, and can be used for preparing CoCl 2 K after molding v The total channel current was raised to 73.40% of the blank.
4. Salidroside pair for regulating potassium ion channel subtype K v 2.1 channel effects, test methods and "3. Salidroside affects H9c2 cell K v The method in the total channel current "is approximately the same. The method comprises the following specific steps:
(1) The electrode inner liquid is prepared as follows: 0.4100 g KCl (130.0 mM), 0.0406g MgCl 2 （4 mM），0.101 g Na 2 ATP (4 mM), 0.1190g HEPES (10.0 mM), 0.0190 g EGTA (1.0 mM) was added to 50mL pure water, pH was adjusted to 7.2 with 1M KOH, and the mixture was filtered and packaged and then stored to-20deg.C;
(2) The extracellular fluid is prepared as follows: 0.0185 g KCl (5.0 mM), 0.3798g NaCl (130.0 mM), 0.0203 g MgCl 2 （2.0 mM），0.119 g HEPES （10 mM），0.0555 CaCl 2 (10.0 mM), 0.0990 g of D-glucose (10.0 mM) was added to 50mL pure water, pH was adjusted to 7.4 with 1M NaOH, and the mixture was filtered and stored to 4 ℃;
(3) 1M citalopram (cit., K) v 2 channel inhibitor) mother liquor is formulated as: 20 mg citalopram was added to 616.54. Mu.L DMSO solution. The mother liquor was diluted to 50 mM with extracellular fluid in the bath.
(4) The stimulation procedure for current recording was: the clamping voltage of the cells is-60 mV, the cell membrane voltage is clamped at-60 mV, the cells are stimulated by rising from-80 mV to +80mV in a Ramp mode of 150 ms per rising 10 mV, and the current interval time of each string is 220 ms.
(5) Experimental results: the decrease in current density of H9c2 cells under the influence of citalopram, recorded from fig. 17, indicates that the whole cell patch clamp technique detection can record kv2.1 channel current. The results in FIGS. 17-23 show that salidroside is effective on blank H9c2 cells K v 2.1 channel current also shows inhibition effect, and the inhibition effect is strongest when the administration concentration is 20-40 mu M, and the inhibition effect is largest when the voltage is +60mVThe preparation rate is 47.71%; while figures 24-29 show: 300. mu M CoCl 2 Predosing 24H on H9c2 cells K v 2.1 channel current has inhibition effect, average inhibition rate is 61.12% at +60mV voltage, and CoCl can be reduced after administration of salidroside 2 For H9c2 cell K v 2.1 channel current, and the effect is concentration dependent, and the effect is strongest when the concentration of salidroside is 80 mu M, so that Kv2.1 channel current after molding citalopram can be improved to 79.88% of a blank group.
In conclusion, the invention is proved by a cell test: salidroside for normal myocardial cell K v Total channel and K v 2.1 the current in the channel is inhibited and K is inhibited in the anoxic state v Total channel and K v 2.1 myocardial cells with suppressed channel currents have an ameliorating effect, which results in K v Total channel and K v The 2.1 channel current can be restored to normal level. Use of salidroside for preventing and/or treating myocardial cell K + The heart ion channel diseases caused by the abnormality of the ion channel, in particular to the long QT syndrome, have good effects and have practical clinical popularization and application values.

Claims (10)

1. Use of salidroside in preparing medicine for preventing and/or treating heart ion channel diseases is provided.
2. The use according to claim 1, wherein the cardiac ion channel disorder comprises long Q-T interval syndrome, short Q-T interval syndrome, brugada syndrome or catecholamine sensitive polymorphic ventricular tachycardia.
3. The use according to claim 1, wherein the cardiac ion channel disorder is long Q-T interval syndrome.
4. The use according to claim 1, wherein the medicament is for inhibiting normal cardiomyocyte K v Drug of total channel current.
5. According to claim4, wherein the agent inhibits normal cardiomyocyte K v 2.1 channel current drug.
6. The use according to claim 1, wherein the medicament is for enhancing hypoxic cardiomyocyte K v Drug of total channel current.
7. The use according to claim 6, wherein the medicament is for enhancing hypoxic cardiomyocyte K v 2.1 channel current drug.
8. The use according to any one of claims 1 to 7, wherein the medicament is a preparation prepared by adding pharmaceutically acceptable auxiliary materials or auxiliary components to salidroside as an active ingredient.
9. The use according to claim 8, wherein the formulation is an oral formulation.
10. The use according to claim 9, wherein the oral formulation is a solution, a granule, a pill, a paste, a tablet or a capsule.
CN202311202796.4A 2023-09-18 2023-09-18 Application of salidroside in preparing medicine for treating heart ion channel diseases Pending CN116942686A (en)

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