CN108478594B - 岩藻多糖在制备防治有机磷农药所致胚胎毒性的药物中的应用 - Google Patents
岩藻多糖在制备防治有机磷农药所致胚胎毒性的药物中的应用 Download PDFInfo
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Abstract
本发明涉及岩藻多糖的一种医药新用途,即预防与治疗有机磷农药所致的胚胎毒性作用,以及抑制因有机磷农药所致胚胎活胎率下降、胚胎死胎率或吸收胎率升高、胎盘重量下降的作用。本发明经药理学试验验证,岩藻多糖能抑制有机磷农药(如久效磷和辛硫磷)所致的孕鼠活胎数、活胎率下降和死胎率、吸收胎率升高及活胎鼠的体重、体长、尾长、胎盘重量的下降,岩藻多糖能抑制有机磷农药的胚胎毒性,有较好的剂量依赖性。岩藻多糖对有机磷农药所致胚胎毒性具有良好的抑制作用,可用于制备防治有机磷农药所致胚胎毒性的药物,还可用于制备预防和治疗因有机磷农药所致胚胎毒性诱发的疾病的药物。
Description
技术领域
本发明涉及岩藻多糖的应用,具体涉及岩藻多糖在制备预防与治疗因有机磷农药所致胚胎毒性疾病的药物中的应用。
背景技术
有机磷农药(OPs)是一类高效、低残留的农药,已经成为当今中国使用的最广谱农药。有机磷农药的使用为农、林、渔业的增产丰收立下了汗马功劳,但随着有机磷农药的广泛使用,其在蔬菜水果等食物中的残留现象也较为普遍。虽然大多数人已经注意预防有机磷农药的急性中中毒,但有机磷农药的长期、低剂量、慢性暴露对人类健康的影响,尤其是孕妇暴露对后代的影响,还未引起人们的足够重视。国内外流行病学研究发现,在长期遭受有机磷农药污染的地区或者农药厂的工人,女性***改变、流产增多、胎儿宫内发育迟缓、卵巢癌和乳腺癌发病率升高(Arbuckle TE,Lin Z,Mery LS,et al.An exploratoryanalysis of the effect of pesticide exposure on the risk of spontaneousabortion in an ontario farm population.Environ Health Perspect,2001,109:851-857.)。我们和国内外多位学者的研究发现,有机磷农药具有胚胎毒性,有机磷农药暴露,可导致怀孕小鼠,体重增加减少,活胎数减少,死胎和吸收胎数增多,仔代出生体重下降,发育迟缓,畸形(FaragAT,Karkour TA,El-OkazyA.Developmental toxicity of orallyadministered technical dimethoate in rats.Birth Defects Res B DevReprodToxicol,2006,77:40-46.)。因此探讨有机磷农药的胚胎毒性作用机制,寻找有限的干预药物,对于保护我国人民的身体健康至关重要。
岩藻多糖(Fucoida)又称褐藻糖胶、岩藻多糖硫酸酯,是存在于所有褐藻中的一种水溶性杂多糖。大量科学研究表明,岩藻多糖具有广泛的生理生化活性,岩藻多糖具有双向调节免疫力,可清除自由基,抗衰老,抗凝血和抗血栓,抗肿瘤和抗病毒,可消除胃肠***紊乱,抗过敏,增强肝功能,降低高血脂和高血压,稳定血糖水平,并具有促进肌肤再生、皮肤保湿等多种生理功效。岩藻多糖无任何毒副作用,可以长期服用。
发明内容
本发明的目的在于提供岩藻多糖在制备防治有机磷农药所致机体损伤方面的药物新用途。
具体的说,本发明涉及岩藻多糖在制备防治有机磷农药所致胚胎毒性的药物中的应用。
此外,还涉及岩藻多糖在制备预防与治疗因有机磷农药所致胚胎毒性诱发的疾病的药物中的应用。
其中所述疾病为因有机磷农药所致的胚胎毒性疾病,主要包括:死胎、胚胎畸形、胚胎生长迟缓、出生缺陷、子宫疾病、胎盘疾病等。
本发明所述有机磷农药为久效磷、辛硫磷、对氧磷、***磷等常用有机磷农药。
本发明所属药物是指以岩藻多糖为主要活性成分,与可药用载体制成的医疗上可接受的制剂,如片剂、丸剂或胶囊剂等。
本发明通过动物实验研究发现:服用岩藻多糖可达到防治有机磷农药所致胚胎毒性的效果,起到抑制因有机磷农药所致的胚胎活胎率下降、胚胎死胎率或吸收胎率升高、胎盘重量下降的一系列问题。岩藻多糖的治疗有效量,应按照治疗者的年龄、身体状况、接触有机磷农药量等确定。
本发明所述的岩藻多糖具有免疫调节活性,能起到抗肿瘤、抗氧化、抗病毒、抗凝血、抗过敏等作用,并且目前尚未发现其有任何毒副作用。岩藻多糖可以通过市售得到,也可以通过多种方法提取获得,提取方法成熟。
本发明人以高毒有机磷农药久效磷和低毒有机磷农药辛硫磷为代表,研究了有机磷农药的胚胎毒性作用,发现有机磷农药的胚胎毒性作用主要是引起孕鼠吸收胎率和死胎率升高、每窝活胎数减少;活胎鼠体重、身长、尾长和胎盘重量下降,从而引起如胎儿出生畸形、流产、死胎、胚胎生长迟缓、出生缺陷等一系列疾病。
本发明通过动物实验观察了有机磷农药对小鼠的胚胎毒性作用,以及岩藻多糖对有机磷农药胚胎毒性的抑制作用。经研究发现,岩藻多糖能抑制(如久效磷和辛硫磷)有机磷农药所致的孕鼠活胎数、活胎率下降和死胎率、吸收胎率升高及胎鼠的体重、体长、尾长及胎盘重量的下降,岩藻多糖能抑制有机磷农药的胚胎毒性,有较好的剂量依赖性。
本发明的有益效果在于:
1.本发明提供了有机磷农药对机体胚胎毒性作用的直接证据,并以此寻找有效的干预药物。
2.本发明提供了岩藻多糖的医药新用途,其对有机磷农药引起的胚胎毒性具有很好的抑制和保护作用。岩藻多糖能抑制有机磷农药(如久效磷)所致的孕鼠体重增加减少、吸收胎率和死胎率升高,每窝活胎数减少、活胎鼠体重、身长、尾长和胎盘重量下降,有良好的剂量依赖性。
3.本发明对长期接触有机磷农药的人尤其是孕妇具有深远的意义,能起到保护孕妇及其子代身体健康、提高生活质量、降低***不育、优生优育、延长寿命等作用。
具体实施方式
以下通过试验例来进一步阐述本发明中岩藻多糖的医药新用途及其有益效果,但不用来限制本发明的范围。
试验例1:岩藻多糖抑制久效磷所致胚胎毒性的试验研究
1材料与方法
1.1材料
久效磷(40%制剂,青岛农药厂),岩藻多糖(中国海洋大学惠赠)。
1.2实验动物及分组
选择健康SPF级性成熟昆明小鼠120只,体重在(25±2)g之间,雌︰雄为2︰1,购自桂林医学院动物实验中心。适应性饲养7d,室温(25±2)℃,湿度50%-55%。
将小鼠按雌︰雄为2︰1合笼交配,次日早晨检查雌鼠有无阴栓,无阴栓的雌鼠用浸湿生理盐水的棉签取***分泌物涂于含有一滴生理盐水的载玻片上,在低倍镜下检查有无***。发现阴栓或***的当天定为孕期第0天。将授精雌鼠随机分为6组,每组15只。分别为正常对照组(A)、岩藻多糖对照组(B)、久效磷对照组(C)、岩藻多糖低剂量保护组(D)、岩藻多糖中剂量保护组(E)。其中对照组(A)不给药,给予蒸馏水,岩藻多糖对照组(B)给予岩藻多糖1g/kg,久效磷对照组(C)给予0.20mg/kg,岩藻多糖低剂量保护组(D)给予岩藻多糖0.5g/kg+久效磷0.20mg/kg,岩藻多糖中剂量保护组(E)给予岩藻多糖1g/kg+久效磷0.20mg/kg,岩藻多糖高剂量保护组(F)给予岩藻多糖2g/kg+久效磷0.20mg/kg。并保证充足的饮水和饲料供应,授精鼠当日称重。在孕期采用灌胃方式进行染毒,染毒剂量为10ml/kg,每天1次。
1.3统计学方法
采用SPSS 10.0软件进行统计学分析。计量资料实验数据均以x±s进行表示,多组间比较采用方差齐性检验和单因素方差分析(One WayANOVA)。进一步进行组间两两比较时,若方差齐时,采用SNK检验;若方差不齐时,采用Games-Howell检验。计数资料实验数据均以率表示,组间两两比较采用χ2检验。以P<0.05为差异有统计学意义。
2方法与结果
于孕期第20天,处死孕鼠,剖开腹腔取出子宫,记录子宫重量、活胎数、死胎数(含早期及晚期死胎)和吸收胎数。取胎鼠和胎盘,称活胎鼠体重和胎盘重,测量体长、尾长。结果如表1和2所示。
表1岩藻多糖对久效磷所致孕鼠子宫重量及活胎数、活胎率下降和死胎率、吸收胎率升高的保护作用(n=15)
注:与A组比较:*P<0.05,与C组比较:△P<0.05。
表1显示,与正常对照组(A)相比,久效磷对照组(C)活胎数和活胎率均下降,死胎率和吸收胎率均升高,差异有统计学意义(P<0.05)。岩藻多糖保护组能抑制久效磷染毒引起的孕鼠活胎数、活胎率下降和死胎率、吸收胎率升高,以岩藻多糖高剂量保护组(F)作用最显著,岩藻多糖高剂量保护组(F)活胎数、活胎率和死胎率、吸收胎率,与久效磷对照组(C)相比有显著差异(P<0.05),与正常对照组(A)相比,没有显著差异(P>0.05)。
表2岩藻多糖对久效磷所致胎鼠体重、体长、尾长、胎盘重量下降的保护作用(n=15)
注:与A组比较:*P<0.05,与C组比较:△P<0.05。
表2可见,与正常对照组(A)相比,久效磷磷对照组(C)胎鼠的体重、体长、尾长及胎盘重量均下降,差异有统计学意义(P<0.05)。岩藻多糖保护组能抑制久效磷染毒引起的胎鼠的体重、体长、尾长及胎盘重量下降,以岩藻多糖高剂量保护组(F)作用最显著,岩藻多糖高剂量保护组(F)胎鼠的体重、体长、尾长及胎盘重量,与久效磷对照组(C)相比有显著差异(P<0.05),与正常对照组(A)相比,没有显著差异(P>0.05)。
试验例2:岩藻多糖抑制辛硫磷所致胚胎毒性的试验研究
1材料与方法
1.1材料
辛硫磷(40%乳油,山东东泰农化有限公司),岩藻多糖(中国海洋大学生命学院惠赠)。
1.2实验动物及分组
选择健康SPF级性成熟昆明小鼠120只,体重在(25±2)g之间,雌︰雄为2︰1,购自桂林医学院动物实验中心。适应性饲养7d,室温(25±2)℃,湿度50%-55%。
将小鼠按雌︰雄为2︰1合笼交配,次日早晨检查雌鼠有无阴栓,无阴栓的雌鼠用浸湿生理盐水的棉签取***分泌物涂于含有一滴生理盐水的载玻片上,在低倍镜下检查有无***。发现阴栓或***的当天定为孕期第0天。将授精雌鼠随机分为6组,每组15只。分别为正常对照组(A)、岩藻多糖对照组(B)、辛硫磷对照组(C)、岩藻多糖低剂量保护组(D)、岩藻多糖中剂量保护组(E)。其中对照组(A)不给药,给予蒸馏水,岩藻多糖对照组(B)给予岩藻多糖1g/kg,辛硫磷对照组(C)给予20mg/kg,岩藻多糖低剂量保护组(D)给予岩藻多糖0.5g/kg+辛硫磷20mg/kg,岩藻多糖中剂量保护组(E)给予岩藻多糖1g/kg+辛硫磷20mg/kg,岩藻多糖高剂量保护组(F)给予岩藻多糖2g/kg+辛硫磷20mg/kg。并保证充足的饮水和饲料供应,授精鼠当日称重。在孕期采用灌胃方式进行染毒,染毒剂量为10ml/kg,每天1次。
1.3统计学方法
采用SPSS 10.0软件进行统计学分析。计量资料实验数据均以x±s进行表示,多组间比较采用方差齐性检验和单因素方差分析(One WayANOVA)。进一步进行组间两两比较时,若方差齐时,采用SNK检验;若方差不齐时,采用Games-Howell检验。计数资料实验数据均以率表示,组间两两比较采用χ2检验。以P<0.05为差异有统计学意义。
2方法与结果
于孕期第20天,处死孕鼠,剖开腹腔取出子宫,记录子宫重量、活胎数、死胎数(含早期及晚期死胎)和吸收胎数。取胎鼠和胎盘,称活胎鼠体重和胎盘重,测量体长、尾长。结果如表3和表4所示。
表3岩藻多糖对辛硫磷所致孕鼠子宫重量及活胎数、活胎率下降和死胎率、吸收胎率身高保护作用(n=15)
注:与A组比较:*P<0.05,与C组比较:△P<0.05。
表3显示,与正常对照组(A)相比,辛硫磷对照组(C)活胎数和活胎率均下降,死胎率和吸收胎率均升高,差异有统计学意义(P<0.05)。岩藻多糖保护组能抑制辛硫磷染毒引起的孕鼠活胎数、活胎率下降和死胎率、吸收胎率升高,以岩藻多糖高剂量保护组(F)作用最显著,岩藻多糖高剂量保护组(F)活胎数、活胎率和死胎率、吸收胎率,与辛硫磷对照组(C)相比有显著差异(P<0.05),与正常对照组(A)相比,没有显著差异(P>0.05)。
表4岩藻多糖对辛硫磷所致胎鼠体重、体长、尾长、胎盘重量下降的保护作用(n=15)
注:与A组比较:*P<0.05,与C组比较:△P<0.05。
表4可见,与正常对照组(A)相比,辛硫磷对照组(C)胎鼠的体重、体长、尾长及胎盘重量均下降,差异有统计学意义(P<0.05)。岩藻多糖保护组能抑制辛硫磷染毒引起的胎鼠的体重、体长、尾长及胎盘重量下降,以岩藻多糖高剂量保护组(F)作用最显著,岩藻多糖高剂量保护组(F)胎鼠的体重、体长、尾长及胎盘重量,与辛硫磷对照组(C)相比有显著差异(P<0.05),与正常对照组(A)相比,没有显著差异(P>0.05)。
从以上各实验例可以看出,岩藻多糖能抑制(如久效磷和辛硫磷)有机磷农药所致的孕鼠活胎数、活胎率下降和死胎率、吸收胎率升高及胎鼠的体重、体长、尾长及胎盘重量的下降,岩藻多糖能抑制有机磷农药的胚胎毒性,有较好的剂量依赖性。岩藻多糖对有机磷农药所致胚胎毒性具有良好的抑制和保护作用,可用于制备防治有机磷农药所致胚胎毒性的药物,还可用于制备预防和治疗因有机磷农药所致胚胎毒性诱发的疾病的药物。
虽然,上文中已经用一般性说明、具体实施方案以及试验例对本发明做了详尽的描述,但在本发明的基础上,所属领域的普通技术人员可以对之作一些修改和改进,这对本领域技术人员而言是显而易见的。因此在不偏离本发明精神的基础上,所做的这些修改和改进,均属于本发明要求保护的范围。
Claims (2)
1.岩藻多糖在制备防治有机磷农药所致胚胎毒性诱发的疾病的药物中的应用,其特征在于所述胚胎毒性诱发的疾病为死胎、吸收胎、胚胎生长迟缓、子宫疾病、胎盘疾病。
2.根据权利要求1所述的应用,其特征在于所述有机磷农药为久效磷、辛硫磷、对氧磷或***磷。
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