雷公藤内酯醇抗生育作用的有效性与安全性研究

A Study of the Effectiveness and Safeness of the Antifertility Action of Triptolide in Rats

目的探讨雷公藤内酯醇的抗生育作用部位和安全性。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、肾等的影响。实验分两个阶段,第一阶段给实验组大鼠喂服雷公藤内酯醇0.05 mg.kg-1.d-1[用1%二甲亚砜(DMSO)配制],每周6 d,连续8周,对照组喂服1%DMSO2 mL.kg-1.d-1;第二阶段给实验组大鼠分别喂服雷公藤内酯醇0.10,0.05,0.03 mg.kg-1.d-1,每周6 d,连续8周,对照组喂服1%DMSO2 mL.kg-1.d-1。每周称量体重,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。结果实验组精子活性明显下降,雷公藤内酯醇剂量≥0.05 mg.kg-1.d-1时,大鼠精子活性为0,睾丸内精曲小管生精上皮损伤,管腔内上皮脱落,对照组大鼠形态学观察未见明显异常。实验组与对照组睾丸生精细胞凋亡差异无显著性,不同剂量雷公藤内酯醇对实验组和对照组的体重影响差异无显著性。结论雷公藤内酯醇是一种有效的抗生育药,对组织器官的毒性较小,且避孕作用是可逆性的。

Objective To probe into the site of the antifertility action of triptolide as well as the safeness of its administration in rats . Methods Thirty healthy male Wistar rats were used to study the impact of triptolide on spermatogenesis and histology of the testicle, epididymis and visceral organs, including the heart, liver , kidney etc.. The course of the experiment was divided into two stages. 6 animals used in the first stage were randomly divided into 2 equal groups . Rats of the trial group 1 （ n = 3 ） were given each 0. 05 mg·kg^-1 of triptolide [ dissolved in 1% dimetlyl sulfoxide （ DMSO ） ] administered by gastrogavage q.d. in 6 days of a week for 8 consecutive weeks. Rats of the control group 1 （ n = 3 ） were given each 2 mL·kg^-1 of 1% DMSO in the same manner and duration as described above. 24 rats used in the second stage of the experiment were randomly divided into 4 equal groups with 6 animals in each group. Rats of the trial groups 2, 3 and 4 were given each 0. 10,0.05 and 0.03 mg·kg^-1 of triptolide administered by gastrogavage q.d. , respectively ,in 6 days of a week for 4 consecutive weeks. Rats of the control group 2 were given 1% DMSO 2 mL·kg^-1·d^-1 in the same manner and duration. The animals were weighed every week, and tissues were taken for studying the state of apoptosis of the testicular spermatogenic cells, vitality of epididymal spermatozoa and histology of the heart, liver, kidney and testicle. Results Vitality of the spermatozoa in rats of the trial groups was significantly decreased. No vitality （ zero vitality） of the spermatozoa was demonstrated when the dosage of triptolide was≥0.05 mg·kg^-1·d^-1, Seminiferous epithelium of the convoluted seminiferous tubules was injured, with exfoliation of the luminal epithelium. No remarkable morphological anomaly was found in the relevant organs in rats of the control groups. The difference between rats of the trial groups and control groups with respect to the state of apoptosis of testicular spermatogenic cells was insignificant , as demonstrated by flow cytometry. The difference between body weights in rats of the controls groups and those of the trial groups treated with different doses of triptolide was insignificant as well. Conclusion Triptolide was shown to be an effective antifertility drug with trivial tissue toxicity , and its contraceptive effect is reversible.