CN101897952A - Application of trefoil factor 3 to preparing medicament for preventing and/or treating depressive disorder - Google Patents
Application of trefoil factor 3 to preparing medicament for preventing and/or treating depressive disorder Download PDFInfo
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- CN101897952A CN101897952A CN 201010217952 CN201010217952A CN101897952A CN 101897952 A CN101897952 A CN 101897952A CN 201010217952 CN201010217952 CN 201010217952 CN 201010217952 A CN201010217952 A CN 201010217952A CN 101897952 A CN101897952 A CN 101897952A
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Abstract
The invention discloses new application of a trefoil factor 3 and provides application of the trefoil factor 3 for preparing a medicament for preventing and/or treating depressive disorder. The product is a medicament. For mainly discovering that the TFF3 has the antidepressant action, the invention can be used for preventing and treating the depressive disorder caused by various factors.
Description
Technical field
The present invention relates to the new medicinal usage of a kind of trefoil factor 3.
Background technology
Depression (depression) is a kind of mental sickness occurred frequently, and the patient shows as lasting depressed and cognitive disorder.WHO infers that the whole world has 3.4 hundred million patients with depression approximately at present, will become the primary disease that the mankind are disabled to the year two thousand twenty depression.Depression has also brought heavy social burden in serious reduction patient life quality. and survey result shows that the economic loss that China causes because of depression is about 51,000,000,000 yuans, and in the U.S., the loss that depression causes is about 44,000,000,000 dollars every year.In addition, chronic disease (as diabetes, cardiovascular disease) is suffered from social economy's burden that depression causes altogether and still can be continued to increase the weight of.Research depression pathogeny and development new method are very urgent with the treatment depression with the new way prevention, have great national interests demand and important scientific meaning.
Traditional view thinks that the depression pathogeny is relevant unusually with the interior monoamine neurotransmitter of born of the same parents, and the antidepressant drug of developing at this viewpoint mainly comprises: monoamine re-uptake inhibitor, oxidase inhibitor, receptor antagonist, plant amedica etc.Very important is, although it is slow and have a patient's rebound phenomenon repeatedly that continues to take medicine that existing most antidepressant drugs show as curative effect of medication jointly. novel antidepressant is extensive use of clinically, and tricyclic antidepressant still occupies critical role in the treatment of depression.But the tricyclic antidepressant therapeutic index is narrow and small, excessive use produces serious toxicity (after one's own heart dysentery), even cause sudden death, untoward reaction also comprise take medicine that the back is calm, drowsiness, weight increase, hypotension, memory impairment, constipation, blurred vision, xerostomia etc.The domestic existing antidepressants mostly are import or imitated, though imitated medicine cost is low, the market of occupying is limited, does not also have very strong international competitiveness.The simple therapeutic effect of Chinese medicine compound antidepressant drug is undesirable, also needs to share with Western medicine.Therefore, urgent need will be researched and developed new and effective antidepressant drug.
Trefoil factor 3 (TFF3, or intestine trilobate factor, intestinal trefoil factor (ITF)); Or human intestine trilobate factor, human intestinal trefoil factor (HITF)) be a kind of aprotinin, it produces in the small intestinal goblet cell usually, in normal breast epithelium, uterus and some body of gland expression is arranged also.Be secreted into enteric cavity (Thim etc., Biochemistry, nineteen ninety-five, 34,4757) after from goblet cell, expressing.TFF3 brings into play function (Mashimo etc. in the recovery of damage epithelium posterius; Science; 1996,274,262 and Wong etc.; Biochemistry; nineteen ninety-five, 34,4757); protection of participation gastrointestinal tract mucosa and damage are expressed the back reparation and are had important function, and closely related with generation, the development of tumor.Reorganization TFF3 be proposed to be used in the treatment that relates to irritable bowel syndrome and other intestinal diseases (referring to, as, U.S. Patent number 6063755,6316218 etc., China Patent No. CN1742996, CN101100690, CN1871033 etc.), cancer (referring to, as, CN101152563, CN1655675 etc.).
Summary of the invention
The purpose of this invention is to provide a kind of trefoil factor 3 and prevent and/or treat purposes in the depression medicine in preparation.
The invention provides trefoil factor 3 and prevent and/or treat application in the depression product in preparation.Described product is a medicine.
Described trefoil factor 3 can be people source or animal origin or the recombinant expressed trefoil factor 3 of genetic engineering.
The aminoacid sequence of described trefoil factor 3 is the sequence 1 in the sequence table.
The depression that the present invention mentioned comprises unipolar depression and two-phase depression clinically.
The present invention has found that mainly TFF3 has antidepressant effect, therefore, can be used for preventing and/or treating the depression that is caused by various factors.
Description of drawings
Fig. 1 is the model flow chart
The flotation time that Fig. 2 significantly reduces the forced swimming experiment mice for TFF3.
Fig. 3 is the dead time that TFF3 significantly reduces outstanding tail experiment mice.
Fig. 4 does not change the spontaneous activity of mice for TFF3.
The specific embodiment
Employed experimental technique is conventional method if no special instructions among the following embodiment.
Used material, reagent etc. if no special instructions, all can obtain from commercial channels among the following embodiment.
Laboratory animal adopts male mice in kunming (available from Department Of Medicine, Peking University's Experimental Animal Center, animal credit number 013056)
The intestine trilobate factor of recombinant rat is (available from the good letter in Yongkang, Beijing Bioisystech Co., Ltd, batch number: 002010011101, the aminoacid sequence of the intestine trilobate factor of described recombinant rat is the sequence 1 in the sequence table) be dissolved in 0.9% normal saline, intraperitoneal injection; Desmethylimipramine (DMI is available from sigma company) adopts the subcutaneous injection administration.
The mice drinking-water of freely ingesting is normally raised after 5 days and is begun administration, the about 25-30 gram of body weight during experiment, the test of administration laggard capable behavioristics half an hour.
Mice is divided into seven groups at random, 12 as one group, inject 0.9% normal saline, 0.01mg/kgTFF3,0.1mg/kg TFF3,0.5mg/kg TFF3,1.0mg/kg TFF3,2.0mg/kg TFF3,15mg/kg desmethylimipramine (desipramine respectively with these 7 groups, DMI), constitute negative control solvent group, 0.01mg/kg TFF3 group, 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group, 2.0mg/kg TFF3 group and DMI positive controls.Fig. 1 is the administration flow chart.
The swimming device is made (the high 24cm of glass jar, diameter 15cm, depth of water 17cm, 24 ± 2 ℃ of water temperatures) by transparent organic glass rat is placed in one, and adapts to after 1 minute, writes down the floating dead time of mice in 5 minutes.The floating dead time is defined as the little body of curling up of mice, is the time of floating state (the forced swimming experiment is classical antidepressants screening model, and effectively antidepressants can reduce the floating dead time of mice swimming).
Experiment repeats 3 times, and experimental result is represented with mean+/-standard error, handles with the t inspection statistics.
The floating dead time of mice of negative control solvent group, 0.01mg/kg TFF3 group, 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group, 2.0mg/kg TFF3 group and DMI positive controls was respectively 176 ± 19 seconds, 64 ± 11 seconds, 33 ± 10 seconds, 152 ± 18 seconds, 167 ± 18 seconds, 165 ± 20 seconds, 59 ± 11 seconds.
Result's statistics as shown in Figure 2, as seen from Figure 2, compare with the solvent matched group, 0.01,0.1mg/kg TFF3 group can significantly reduce the floating dead time of mice (p＜0.001), compare with positive controls, 0.01mg/kg TFF3 group does not have significant difference, 0.1mg/kg TFF3 group can the more significant floating dead time of reduction mice (p＜0.001), illustrates that the intestine trilobate factor of recombinant rat has significant antidepressant effect.* is P＜0.001 and solvent matched group ratio among the figure, §: p＜0.005 and positive controls (DMI).
Mice after the administration among the embodiment 1 is carried out another laboratory observation: mice is hung upside down (document European Journal of Pharmacology last 6 minute of cross bar in distance ground 60cm, 2001,415:197), the fixedly site of mice is apart from tail 1cm place slightly, the 1st minute is the laundering period, mouse tail suspension behavior observation instrument is observed back 5 minutes mice dead times, motionless state is defined as mice to be stopped to struggle, body is relaxation state, and (the mouse tail suspension experiment is classical screening antidepressants experimental model, mouse tail suspension presents desperate state after a period of time, stop to struggle.Effectively antidepressant drug can make dead time shortening in the mouse tail suspension process).
The experiment triplicate, experimental result is represented with mean+/-standard error, handles with the t inspection statistics.
The mice dead time (second) of negative control solvent group, 0.01mg/kg TFF3 group, 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group, 2.0mg/kg TFF3 group and DMI positive controls is respectively 169 ± 35,151 ± 26,77 ± 17,72 ± 23,102 ± 22,140 ± 38,89 ± 15.
Result's statistics as shown in Figure 3, as seen from the figure, compare with the solvent matched group, 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group all can significantly reduce the mice dead time (p＜0.005), comparing with positive controls does not have significant difference, and the result shows that the rat intestine trefoil factor of reorganization has significant antidepressant effect.
Embodiment 3, TFF3 do not change the spontaneous activity of mice
Mice after the administration among the embodiment 1 is carried out another laboratory observation: mice is put in the spontaneous activity detector, observe spontaneous activity in mice situation in 10 minutes (number of times promptly shuttles back and forth), the experiment triplicate, the result represents with mean+/-standard error, handles with the t inspection statistics.
The number of times that shuttles back and forth of negative control solvent group, 0.01mg/kg TFF3 group, 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group, 2.0mg/kg TFF3 group and DMI positive controls is respectively 377 ± 76,300 ± 34,332 ± 38,333 ± 33,355 ± 67,332 ± 48,291 ± 20.
Result's statistics shows as shown in Figure 4, compares with positive controls with the solvent matched group, and 0.1mg/kg TFF3 group, 0.5mg/kg TFF3 group, 1.0mg/kg TFF3 group, 0.01mg/kg TFF3 group, the spontaneous activity of 2.0mg/kg TFF3 group all do not have significant change.Proof, the TFF3 administration is free from side effects to mice.
From above-mentioned experiment as can be seen, TFF3 can be used as the depression that antidepressant drug is treated mice.
Claims (2)
1. trefoil factor 3 prevents and/or treats application in the depression product in preparation.
2. application according to claim 1 is characterized in that: described product is a medicine.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010102179520A CN101897952B (en) | 2010-06-24 | 2010-06-24 | Application of trefoil factor 3 to preparing medicament for preventing and/or treating depressive disorder |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526702A (en) * | 2010-12-23 | 2012-07-04 | 中国医学科学院基础医学研究所 | Small peptide trefoil factor family 3 (TFF3) for curing metabolic syndrome |
-
2010
- 2010-06-24 CN CN2010102179520A patent/CN101897952B/en active Active
Non-Patent Citations (4)
| Title |
|---|
| 《ARCH.GEN.PSYCHIATRY》 19960229 Jan S.Purba et al. increased number of vasopressin-and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression 137-143 1,2 第53卷, * |
| 《The FASEB Journal》 20001231 WOLFGANG JAGLA et al. co-localization of TFF3 peptide and oxytocin in the human hypothalamus. 1126-1131 1,2 第14卷, 第9期 * |
| 《上海精神医学》 20091231 杨福中 施慎逊 强迫游泳实验研究应用及进展 188-190 1,2 第21卷, 第3期 * |
| 《动物学研究》 20100228 杜廷义 等 三叶因子：从实验研究到临床医学 17-26 1,2 第31卷, 第1期 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526702A (en) * | 2010-12-23 | 2012-07-04 | 中国医学科学院基础医学研究所 | Small peptide trefoil factor family 3 (TFF3) for curing metabolic syndrome |
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