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

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 MnCl_2)和高剂量(30 mg/kg MnCl_2)组,腹腔注射MnCl_2 4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。

Regulatory effects of XIAP and Smac on the expression of apoptosis protease in spermatogenic cells of rats exposed to manganese

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.