镉诱导腺垂体细胞凋亡与半胱天冬酶信号变化初探  

The effect on apoptosis in anterior pituitary induced b y cadmium chloride and its relations with caspase-9 pathway

作　　者：朱伟[1] 杨杏芬[1] 魏青[1] 林忠宁[1] 郑树声[2] 赵敏[3] 

机构地区：[1]中山大学公共卫生学院预防医学系 [2]中山大学分子医学中心图像分析室 [3]广东省疾病预防控制中心

出　　处：《中华预防医学杂志》2005年第2期115-118,共4页Chinese Journal of Preventive Medicine

基　　金：广东省自然科学基金资助项目(021990)

摘　　要：目的　了解氯化镉诱导腺垂体细胞凋亡发生及半胱氨酸天冬氨酸特异性蛋白酶(procaspase- 9)mRNA表达的变化,为阐明镉致腺垂体毒作用的分子机制提供科学依据。方法　在整体实验中,将健康雄性SD大鼠 48只,分为 4组,每组 12只,分别每天经口灌胃给予 0、1 .0、2 .0、4. 0mg/kg氯化镉, 6周后进行腺垂体激素促肾上腺皮质激素、黄体生成素、卵泡刺激素水平、超微结构、原位末端标记(TUNEL)法检测细胞凋亡及procaspase 9mRNA表达检测;离体实验采用酶解分离大鼠之原代腺垂体细胞, 37℃、5%CO2 条件下培养 120h后分别以 0、1. 56、3 .12、6 .25、12.50、25 .00、50 .00、100 00μmol/L氯化镉处理 6h,收获细胞以TUNEL法检测细胞凋亡及原位杂交法检测procaspase- 9mRNA表达。结果　整体实验表明氯化镉作用后 3个剂量组血中促肾上腺皮质激素、黄体生成素和 1 0mg/kg氯化镉剂量组卵泡刺激素水平均降低,腺垂体细胞呈现明显的凋亡征象;整体和离体实验结果均显示氯化镉以剂量依赖方式诱导腺垂体细胞procaspase- 9mRNA表达的增强,且可使凋亡细胞增多,与对照组比较,差异均具有统计学意义。结论　在一定剂量条件下,氯化镉影响腺垂体激素分泌水平改变,并诱发腺垂体细胞凋亡,caspase -9通路在凋亡发生过程中可能发挥了一定的作?Objective To study the effe ct s of cadmium chloride in anterior pituitary and the relation between apoptosis a nd expression of procaspase-9mRNA.Methods In vivo studi es:40 SD male rats were randomly distributed into four groups which were adminis tered with CdCl 2 at different doses by gavage for 6 weeks; In vitro studies: t he rats’anterior pituitary cells were primarily cultured for 120 hours, then tr eated with CdCl 2 at the dose of 0,1.56,3.12,6.25,12.50,25.00,50.00 ,100.00 μmol/L for 6 hours; The indices included: expression of procaspase-9 mRNA, detection of apoptosis with TUNEL assay.Results T he results showed the excretion of ACTH,LH seemed to be decreased dramatically a nd the apoptosis inclined to enhance remarkably, and further more, the expressio n of procaspase-9 mRNA appeared to be increased significantly as compared with those of the control.It was show that a dose-effect relationship between the CdCl 2 dosing and indices above with the regression analysis and a linear corre lation between the mean gray value of apoptosis cell and the relative gray value of procaspase-9 mRNA positive cell.The results indicated that damnification, for example, apoptosis could be caused by certain dose of CdCl 2 in anterior p ituitary cells with dose dependent manner.Caspase-9 might play a role in the occurrence of apoptosis.Conclusion It was suggested that cadmium could induce apoptosis of anterior pituitary both in vivo and in vitro in the manner of dose-dependent, and caspase-9 might play a role during above processes.

关 键 词：腺垂体细胞 氯化镉 CASPASE-9 凋亡 MRNA表达 诱导 剂量 水平 整体 初探 

分 类 号：R114[医药卫生—卫生毒理学]