复方雷公藤汤对肾病大鼠减毒增效作用的基础研究

How to effect the implementation of outstanding attenuated efficiency of toxic traditional Chinese medicine, is placed in front of a major academic subjects. The subject of toxic effects to be used triptolide attenuated efficiency of excellence as a model to establish the compatibility of traditional Chinese medicine theory and compatible with modern pathology, toxicology knowledge to achieve a small toxic drugs attenuated synergistic combination drug group side selection method, the establishment of a small compound with toxic effects of drug toxicity evaluation of the relationship approach. The subject of compound decoction and its disassembled prescriptions from triptolide attenuated both efficiency studies, examine the compatibility of triptolide on nephropathy in rats of different body weight, 24-hour urine protein, TP, ALB, chol, TG, nephrin and podocin mRNA in renal tissue , protein expression synergies, attenuated in the blood test WBC, PLT, Hb, RBC, liver ALT, AST, kidney UREA, CREA, cardiac CK, CK-MB and heart, liver, kidney cells were cultured in vitro indicators of change. From light microscopy, electron microscope examination of the compatibility group of triptolide heart, liver, kidney attenuated synergies, experimental intervention study the toxic effects of kidney disease, screening the best drug combination attenuated efficiency for toxic Chinese medicine through the attenuated to achieve compatibility of efficiency to provide ideas and methods for clinical applications and drug development to provide experimental basis.

如何对疗效卓著的有毒中药实施减毒增效，是摆在学术界面前的一项重大课题。本课题拟采用毒性较大疗效卓越的雷公藤减毒增效为示范，建立兼容中医配伍理论和现代病理学、毒理学认识以实现含毒性药物小复方减毒增效的选药组方方法，建立含毒性药物小复方毒效关系的评价方法。本课题复方雷公藤汤及其拆方从减毒增效两个方面研究，考查雷公藤不同配伍对肾病大鼠体重、24小时尿蛋白、TP、ALB、chol、TG、肾组织nephrin与podocin mRNA、蛋白表达增效作用，减毒方面考查血WBC、PLT、Hb、RBC，肝脏ALT、AST，肾脏UREA、CREA，心脏CK、CK-MB及 心、肝、肾体外细胞共培养指标的变化。并从光镜、电镜上检验雷公藤各配伍组对心、肝、肾减毒增效作用，考察干预实验性肾病的毒效情况，筛选减毒增效的最佳药物组合，为有毒中药通过配伍实现减毒增效提供思路与方法,为临床应用和新药开发提供实验依据。

雷公藤作为一种传统中药具有清热解毒等功效。对多种难治性疾病有较好的治疗效果，但又对多器官有明确的损害，极大限制了雷公藤在临床上的应用。复方雷公藤汤以肾病综合征为干预对象，基于传统中医配伍理论和现代病理学、毒理学认识，遣药组方。本课题以雷公藤为君药，配伍何首乌、黄芪、当归、金钱草和甘草五味具有相杀、佐制、解毒、调和和扶正作用，且能保护雷公藤毒性靶标的药物，旨在降低雷公藤毒性，提高其疗效。实验结果证明了雷公藤通过不同配伍起到对心、肝、肾、血液系统的减毒增效作用。. 通过本课题的完成达到了建立兼容中医配伍理论和现代病理学、毒理学认识以实现含毒性药物小复方减毒增效的选药组方方法；基于实验筛选出治疗肾病综合征含毒性药物雷公藤的毒效关系最优化的中药小复方。