镉致腺垂体-肾上腺皮质凋亡机制研究

Apoptosis effect of cadmium on anterior pituitary and adrenal cortex

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(1.0 mg/kg)、中剂量组(2.0 mg/kg)、高剂量组(4.0 mg/kg)。经口灌胃染毒,每周5 d,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(westernboltting)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-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。

Objective To study the apoptotic effect of cadmium chloride on anterior pituitary and adrenal cortex and the relations with caspase - 9 signal transductlon passway. Methods 40 SD male rats were randomly distributed into four groups which were adminlsterd with CdC12 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 Apoptesis 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 CAC12 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 apoptesis of anterior pituitary and adrenal cortex in the manner of dose - dependent, and caspase - 9 might play a role during above processes.