镉致腺垂体-肾上腺皮质凋亡机制研究

目的观察CdCl2作用后腺垂体．肾上腺皮质系统凋亡情况及半胱天冬酶-9的表达变化。方法48只雄性SD大鼠随机分为4组，即对照组、CdCl2低剂量组（1．0mg／kg）、中剂量组（2．0mg／kg）、高剂量组（4．0mg／kg）。经口灌胃染毒．每周5d，连续6周。染毒结束后分离腺垂体和肾上腺皮质进行透射电镜观察、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测细胞凋亡、半胱天冬酶原。9mRNA（procaspase-9mRNA）表达、半胱天冬酶-9（caspase-9）表达。结果电镜检查可见凋亡细胞早期形态学变化；中、高剂量组腺垂体和肾上腺TUNEL阳性细胞的平均灰度值和procaspase-9 mRNA阳性细胞相对灰度值均为对照组的1．2倍以上（P〈0．05）；蛋白印迹（western boltting）结果显示，随着染毒剂量的增加，垂体-肾上腺系统caspase-9表达逐渐增强（P〈0．01）。结论CdCl2可诱发腺垂体一肾上腺皮质细胞凋亡，在此过程中caspase-9及其酶原mRNA表达呈现出与凋亡较为一致的趋势。

Apoptosis effect of cadmium on anterior pituitary and adrenal cortex

Objective To study the apoptotic effect of cadmium chloride on anterior pituitary and adrenal cortex and the relations with caspase-9 signal transduction passway.Methods 40 SD male rats were randomly distributed into four groups which were administerd with CdCl2 at different doses by gavage for 6 weeks.The indices included:detection of apoptosis of anterior pituitary and adrenal cortex with electronic microscope,TUNEL assay,expression of procaspase-9 mRNA and caspase-9.Results Apoptosis inclined to enhance remarkably,and the expression of procaspase-9 mRNA and caspase-9 appeared to be increased significantly as compared with those of the control.It was shown that a dose-effect relationship between the CdCl_2 dosage and indices above with the regression analysis and a linear correlation between the mean gray value of apoptosis cell and the level of procaspase-9 mRNA and caspase-9.Conclusion Cadmium could induce apoptosis of anterior pituitary and adrenal cortex in the manner of dose-dependent,and caspase-9 might play a role during above processes.