X连锁凋亡抑制蛋白和线粒体第二激活因子在锰诱导r大鼠生精细胞凋亡蛋白酶表达中的调节作用

摘要

Objective:To determine the regulatory effects of X-linked inhibitor of apoptosis protein (XIAP)and second mitochondria-derived activator of caspases (Smac)on the expression of cysteinyl aspartate specific proteinase-9 (caspase-9)in spermatogenic cells of rats exposed to manganese,and to explore the mechanism of male sterility caused by manganese. Methods:Male rats were divided into one control group and two MnCl2 (15 mg/kg,30 mg/kg)groups.After exposure in manganese for 4 and 6 weeks, the expression of caspase-9 , Apaf-1 , XIAP and Smac in rats were detected by immunohistochemistry.Results:Compared with the blank control,the caspase-9 positive cell rate,the Apaf-1 positive cell rate and the Smac positive cell rate were increased while the XIAP positive cell rate was decreased.Among the same dose and same time manganese groups,the caspase-9 positive cell rate,Apaf-1 positive cell rate and Smac positive cell rate were increased while the XIAP positive cell rate was decreased.There existed a positive correlation between caspase-9 positive cell rate and Apaf-1 positive cell rate,and a negative correlation between XIAP positive cell rate and Smac positive cell rate. Conclusion:Manganese can promote the expression of caspase-9 ,Apaf-1 and Smac,and inhibit the expression of XIAP,which may lead to male reproductive toxicity.%目的:研究氯化锰导致的大鼠生精细胞半胱氨酸天冬氨酸蛋白酶-9(caspase-9)及凋亡蛋白酶活化因子-1(Apaf-1)表达中X连锁凋亡抑制蛋白(XIAP)和线粒体第二激活因子(Smac)的调节机制,探讨锰导致的雄性不育机制.方法:雄性SD大鼠随机分为对照组、低剂量(15 mg/kg MnCl2)和高剂量(30 mg/kg MnCl2)组,腹腔注射MnCl24周和6周,免疫组织化学检测生精细胞caspase-9、Apaf-1、XIAP和Smac表达.结果:与对照组相比较,各组生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低.同时间的高剂量组与低剂量组比较,同剂量的6周组与4周组比较,生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低.各组caspase-9与Apaf-1表达呈正相关,XIAP与Smac表达呈负相关.结论:锰可促进生精细胞caspase-9、Apaf-1和Smac表达,抑制XIAP表达,导致细胞凋亡,产生雄性生殖毒性效应.