金匮肾气丸对肾阳虚大鼠睾丸转化生长因子—β1和细胞色素P—19表达的影响

张晓红等

摘要：目的 观察金匮肾气丸对肾阳虚及转化生长因子-β1（TGF-β1）受体阻滞后大鼠转化TGF-β1、细胞色素P-19（CYP19）、性激素水平和精子质量的影响，并探讨其治疗男性不育的作用机制。方法 将40只成年雄性SD大鼠随机分为正常组、模型组、阻滞剂组、金匮组，每组10只。除正常组外，腺嘌呤混悬液灌胃制备肾阳虚不育模型。正常组给予生理盐水灌胃，阻滞剂组注入大鼠睾丸间质TGF-β1受体阻滞剂，金匮组给予金匮肾气丸水煎剂灌胃。经尾静脉采血并摘取睾丸，采用免疫组化法、放射免疫法和电镜观察，检测睾丸TGF-β1和CYP19的表达、性激素水平、精子密度和活率及睾丸形态学改变。结果 与正常组比较，模型组TGF-β1表达水平升高、CYP19表达水平降低（P<0.05）；与模型组比较，金匮组和阻滞剂组TGF-β1表达水平降低、CYP19表达水平升高（P<0.05）。与正常组比较，模型组大鼠精子数量较少且形态异常（P<0.05）；与模型组比较，金匮组和阻滞剂组睾酮（T）、雌二醇（E2）、精子密度和活率升高（P<0.05）；金匮组和阻滞剂组各项指标比较差异无统计学意义（P>0.05）。结论 金匮肾气丸可改善肾阳虚模型大鼠精子质量和性激素水平，其机制可能是通过抑制睾丸TGF-β1受体表达、促进CYP19表达进而影响精子发育与增殖。

关键词：金匮肾气丸；精子；细胞色素P-19；转化生长因子-β1；大鼠

DOI：10.3969/j.issn.1005-5304.2015.09.020

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2015）09-0072-04

Effects of Jingui Shenqi Pills on Expressions of Testicular TGF-β1 and CYP19 in Kidney-yang-deficiency Rats ZHANG Xiao-hong1， DONG Hai-jun2， WU Lei-tao2， ZHAO Jiao2， CHEN Yan-qiu2， YANG Qian-qian2， MA Jing2 （1.The Second People's Hospital of Jiuquan City， Jiuquan 735000， China；2.Xijing Hospital， Forth Military Medical University of PLA， Xian 710032， China）

Abstract：Objective To observe the effects of Jingui Shenqi Pills on the expressions of TGF-β1， CYP19， sex hormone level and sperm quality；To discuss its mechanism for the treatment of male sterility. Methods Forty adult male SD rats were randomly divided into normal group， model group， retardant group and Jingui Shenqi Pills group， 10 rats in each group. Except for the normal group， adenine was used to induce healthy rats to kidney yang deficiency and sterility model rats. Normal group was given normal saline for gavage；retardant group was injected with testicular mesenchyme TGF-β1；Jingui Shenqi Pills group was given Jingui Shenqi Decoction for gavage. Blood was taken through caudal vein. Immunohistochemical， radioimmunoassay and electron microscopy observation were used to detect the expressions of TGF-β1， CYP19， sex hormone level， sperm density and motility rate and testicular morphological changes. Results Compared with normal group， the expression of TGF-β1 in the model group increased and CYP19 decreased （P<0.05）. Compared with model group， the expression of TGF-β1 decreased and the expression of CYP19 increased （P<0.05）. Compared with normal group， the number of sperm quantity was small and paramorphia in model group （P<0.05）. Compared with model group， T， E2， sperm density and motility rate increased significantly in Jingui Shenqi Pills group and retardant group

基金項目：国家自然科学基金面上项目（30873206）；陕西省中医药管理局重点课题（13-JC049）

通讯作者：马静，E-mail：jingma@fmmu.edu.cn

（P<0.05）. There was no statistical significance among indexes in retardant group and Jingui Shenqi Pills group. Conclusion Jingui Shenqi Pills can improve sperm quality and sex hormone level of model rats with kidney-yang-deficiency， which mechanism is probably realized by inhibiting the expression of TGF-β1R and promoting the expression of CYP19 in testis to effect development and proliferation of sperm.

Key words：Jingui Shenqi Pills；sperm；CYP19；TGF-β1；rats

近年来，男性不育的发病率呈明显上升趋势，并已成为影响人类发展和健康的全球性的医学和社会问题。寻找更有效的药物和方法进行治疗，已成为生殖医学领域里的热点问题。现代研究表明，金匮肾气丸可通过调节下丘脑-垂体-性腺轴的功能，治疗男性少精、弱精[1-3]。前期研究显示，睾丸抑制转化生长因子-β1（TGF-β1）和细胞色素P-19（CYP19）的……