摘要
目的探讨雷公藤多甙对大鼠精子发生的抑制作用及其可能的信号通路。方法成年雄性大鼠给予雷公藤多甙(16 mg/kg)灌胃,每日1次,在2及6周检测血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)和可的松水平;光镜观察睾丸组织的形态学变化;原位末端标记法(TUNEL)观察睾丸生精细胞凋亡;免疫组织化学法观察凋亡通路相关蛋白Bax/Bcl-2的表达。结果给药组与对照组相比,性激素、肾上腺皮质激素均无显著变化(P均>0.05);给药2周后精子数下降和畸形率上升(P<0.05),给药4和6周精子数下降和畸形率升高更显著(P<0.001);组织学检查给药组大鼠生精小管内各级精母细胞和精子细胞数明显减少,生精细胞排列紊乱,原始精原细胞和支持细胞(Sertoli细胞)未见明显改变。与正常对照组相比,生精小管内生精细胞凋亡显著增加(2周P<0.05,4和6周P<0.001)。凋亡相关蛋白Bax表达明显上调,Bcl-2表达无显著差异。结论雷公藤对大鼠精子发生的抑制作用表现为增加生精细胞凋亡,导致精子计数下降,精子的畸形率升高。雷公藤多甙使睾丸Bax表达增加,与诱导生精细胞凋亡相关,可能是相关的信号通路之一。进一步研究雷公藤多甙作用的分子信号机制有助于今后降低剂量、减少毒副作用,探讨其作为一种安全的男性避孕药可能性。
Objectives： Tripterygium wilfordii had been researched as potential male contraceptive for twenty years, however it can not be used in clinic for its poison. It is unclear about its cellular and molecular mechanisms of the suppression of the spermatogenesis. This study was designated to explore the mechanisms of suppression of spermatogenesis induced by Tripterygium wilfordii.
Methods：The thirty SD adult rats were treated with Tripterygium wilfordii （16 mg/kg）by intragastric administration, one time per day. Ten SD adult rats were treated with normal sodium. Testosterones, FSH,LH and cortisol were assayed at two and six weeks. Germ cell apoptosis was evaluated by TUNEL. The expression of Bax/Bcl-2 was analyzed by immunohistochemistry.
Results： Compared to the control group, sperm numbers of the treated groups significantly reduced and the deformed sperm numbers increased when rats were treated after two weeks （P〈0.005）, while being more affected after four or six weeks（P〈0. 001）. The histology revealed that each spermatocytes and spermids obviously reduced, spermatogenic cells arranged chaoticly. The TUNEL revealed that the apoptosis of spermatogenic cells increased significantly. The immunohistochemistry revealed that the expression of Bax was up-regulated.
出处
《生殖医学杂志》
CAS
2008年第2期118-122,共5页
Journal of Reproductive Medicine
基金
江苏省135医学重点人才基金资助(RC2002076)
