雷公藤内酯醇抗生育作用有效性及安全性的研究

雷公藤内酯醇抗生育作用有效性和安全性的研究

研 究 生：徐 元 萍

指导老师：章汉旺 教授

中文摘要

目的：研究雷公藤内酯醇对雄性大鼠的抗生育作用，探讨其作用部位、有效性和毒副作用。

方法：选用健康雄性Wistar大鼠观察雷公藤内酯醇对其精子生成及对睾丸、附睾和心、肝、肾等内脏器官的影响，实验分两个阶段，第一阶段实验组给大鼠喂服雷公藤内酯醇0.05mg/kg·d，每周6d，连续8周, 用1%的二甲基亚砜DMSO 配制，对照组喂服1%二甲基亚砜DMSO，2ml/kg·d，第二阶段实验组给大鼠饲服雷公藤内酯醇0.1mg/kg·d，0.05mg/kg·d，0.03mg/kg·d，每周6d，连续4周，对照组喂服1%DMSO，每周称取体重，取材观察睾丸生精细胞凋亡情况，附睾精子活力及对心、肝、肾、睾丸的影响。

结果：实验组的精子活力明显下降，剂量≥0.05mg/kg·d的大鼠精子活力为0，睾丸切片中，高剂量组有不同程度睾丸生精细胞的损伤，其靶细胞主要为精子细胞和精母细胞，精原细胞未见损害，精子发育停滞，生精小管破坏。睾丸内曲细精管生精上皮有损伤，管腔内上皮有脱落，对照组大鼠形态学观察未见明显异常。应用流式细胞术检测睾丸生精细胞凋亡，实验组与对照组无显著差异，不同剂量的雷公藤内酯醇对实验组和对照组的体重影响并无显著差异。病理切片对照2组及雷公藤内酯醇低、中、高剂量组HE及PAS染色，形态学观察心、肾未见异常，对照2组及雷公藤内酯醇中、低剂量组HE染色，形态学观察肝未见异常，仅大剂量组可见肝细胞少量空泡变性。

结论：雷公藤内酯醇是一种有效的抗生育药，对组织器官的毒性小，且避孕作用是可逆性的，但长时间的使用可引起一定的睾丸及肝脏损伤，作为避孕药推广时尚需对它的成分作进一步的改进研究。

关键词 雷公藤内酯醇 生育力 避孕 大鼠

The Potency and Safety of

Triptolide in Antifertility Action

Postgraduate: Xu Yuanping

Supervisor: Prof. Zhang Hanwang

Abstract

Objective To perform further approach on the site of action and safety of triptolide alcohol in antifertility action.

Methods:Heal thy male Wistar rats were selected to observe the impact of triptolide alcohol on the gonepoiesis and testicle, epididymis and the internal organs, eg.heart, liver and kidney and etc., the experiment was categorized into two phases, in the first phase, the rats of the experimental group were fed with triptolide alcohol 0.05mg/kg·d，6d per week，and continued for 8w, 1% dimethyl sulfoxide DMSO-made，1% dimethyl sulfoxide DMSO was fed in the control group，2ml/kg·d，in the second phase,the rats of the experimental group were fed with triptolide alcohol0.1mg/kg·d，0.05mg/kg·d，0.03mg/kg·d，6d per week，and continued for 4w，the rats of the control group were fed with 1%DMSO，and weighed every week, and draw the materials to observe the state of testicle androgone apoptosis, epididymis azzospermia and the impacts on the heart, liver, kidney and testicle.

Results ：A zzospermia in experimental group was significantly declined, rat azzospermia (dosage≥0.05mg/kg·d) was 0，in vivo testicle contorted seminiferous tubules seminiferous epithelium was damaged, invivo lumens

epithelium had some abation, no morphological anomaly was observed in the rats of control group. testicle androgone apoptosis was detected by flow cytometer, no marked difference was present between experimental group and control group，no significant deviation was found in triptolide alcohol with different dosage in the murine weights of experimental group and control group.

Conclusion：Triptolide was shown to be an effective drug in antifertility and with trivial tissue toxicity,and its contraceptive effect is secure.

Key words Triptolide Fertility Contraception Rats