生远志及其皂苷与蜜远志对胃肠局部激素及酶活性影响机制的研究

【作者】 赵海平；

【导师】 王建；

【作者基本信息】 成都中医药大学 ， 中药学， 2007， 硕士

【摘要】 目的:远志能安神、祛痰、消肿,为临床常用。但使用不当可致“戟喉”、“致呕吐”、“腹胀”、“过敏”等毒性反应。课题组前期研究发现,生远志及其毒性物质皂苷对胃肠有损伤与抑制运动的毒性作用,而蜜远志毒性小,安全性高,达到了减毒存效的目的。为了进一步探讨蜜远志降低胃肠毒性的作用机制,本研究重点考察了生远志及其皂苷与蜜远志对胃肠靶器官激素、递质、ATP酶及相关活性物质的影响;并探索性地考察了对中枢5-HT的影响,为阐释蜜炙降低远志胃肠靶器官毒性机制提供科学依据。方法:以动物实验为主,进行了以下几方面的研究:①采用放射免疫法测定SP、定磷法测定Ca⁺⁺-ATPase活性、硝酸还原酶法测定NO含量,考察了各组药物对胃肠运动抑制机制;②采用放射免疫法测定SS、TBA法测定MDA、羟胺法测定SOD酶活性、荧光分光光度法测定PGE₂,考察了生远志及其皂苷与蜜远志对胃黏膜刺激损伤机制;③采用荧光分光光度法测定5-HT,考察了各组药物的胃肠毒性与中枢神经递质的关系。结果:①生远志组能显著降低胃组织SP含量,而蜜远志组、皂苷组胃组织SP含量则明显高于生远志组（P＜0.05）。②生远志组能显著降低胃组织Ca⁺⁺-ATPase活力（P＜0.05）,且与蜜远志组、皂苷组比较,存在显著性差异（P＜0.05）。③生远志组能显著增加胃组织中NO含量（P＜0.05）,而皂苷组对胃组织NO含量虽有增高趋势,但与空白组比较无显著性差异（P＞0.05）,蜜远志对NO影响不明显。④各给药组胃组织中SS含量显著低于空白组（P＜0.05）。蜜远志组胃组织SS含量显著高于皂苷组P＜0.05)。⑤蜜远志组胃组织MDA含量显著低于生远志组（P＜0.05）。皂苷组MDA含量呈高于蜜远志组趋势。蜜远志组SOD酶活性有增高趋势,但与生远志及其皂苷组相比无明显差异（P＞0.05）。⑥生远志及其皂苷与蜜远志均能显著降低胃组织PGE₂含量（P＜0.05,P＜0.01）,而皂苷更为显著。⑦皂苷组脑组织中5-HT的含量显著高于空白组（P＜0.05）,生远志组5-HT呈升高趋势。结论:①生远志及其皂苷对胃肠运动均呈现显著抑制的毒副反应,其机制与降低胃局部兴奋性神经递质SP含量、减弱Ca⁺⁺-ATPase活性以及增加NO含量相关;而蜜远志的解毒机制与调节、稳定SP、Ca⁺⁺-ATPase活性,进而降低对胃肠黏膜直接刺激损伤有关。②生远志及其皂苷对胃黏膜刺激性损伤与其降低胃黏膜局部防御因子SS、PGE₂,增强氧自由基对胃组织细胞的攻击有关;蜜远志的解毒机制与其调节、稳定SS、PGE₂以及SOD酶活性有关。更多还原

【Abstract】 Objective:Radix Polygalae,can tranquilize the mind,remove phlegm and reduce swelling,as commonly used.Improper use can lead to some toxic reactions,such as guttural stimulus,nausea,distension and allergic reaction.Earlier research found that Radix Polygalae and the toxic substances saponins have toxic effect of injury and inhibition of gastrointestinal movement.Honey-stir-roasted Radix Polygalae is low in toxicity with higher security.This study focus on the effect of gastroenteric target organ hormones,neurotransmitters,ATPase activity and related substances of Crude Radix P,Saponins and Honey-stir-baked Radix P.We also did exploratory studies of the impact of centrums 5-HT,to provide scientific basis for the explanation for the reason why honey-stir-roasting can release the toxicity of the crude Radix P.Method:①determinated SP and SS by RIA,tested enzyme activity of Ca⁺⁺-ATPase by the colorimetric determination of phosphorus,determinated NO by nitroreductase chromatometry,②determined MDA by TBA,determined enzyme activity of SOD by hydroxylamine,determined PGE₂ by fluorescence pectrophotometriy.③determined 5-HT by fluorescence pectrophotometriy.Result:①Crude Radix P can remarkably decrease SP and the activity of Ca⁺⁺-ATPase in gaster tissue and it also can remarkably increase NO in gaster tissue.②Honey-stir-baked Radix P can decrease SS in gaster tissue,but the effect is lower than saponins;MDA in gaster tissue is remarkably lowered in group of Honey-stir-baked Radix P than in group of crude radix P.There is tendency that Honey-stir-baked Radix P can enhance activity of SOD.③Crude Radix P,Saponins and Honey-stir-baked Radix P can remarkably decrease PGE₂ in gaster-tissue, Saponins has the strongest effection;saponins can remarkably increase 5-HT in brain tissue.Conclusion:①Crude Radix P and saponins remarkably inhibit gastrointestinal motility,It may relate to the decrease of SP and activity of Ca⁺⁺-ATP,increase of NO. Detoxification mechanism to inhibition on gastrointestinal motility by Honey-stir- baked Radix P may get the relations to regulate and stable activities of SP and Ca⁺⁺-ATPase.②The stimulus and injury to gastric mucosa by Crude Radix P and saponins may relate to decrease SS,PGE₂,strengthening attack to the gaster tissue cell by oxygen free radicals.The detoxification mechanism of Honey-stir-baked Radix P might relate to regulate and stable SS,PGE₂ and enhance the activity of SOD.更多还原