氯乙烯对大鼠肝细胞P21^(WAF1/CIP1)和P53蛋白表达影响  

Effect of vinyl chloride monomer on P21^(WAF1/CIP1) and P53 protein expression in rat liver cells

作　　者：张盼红[1] 马宁[1] 李阳[1] 张文平[1] 高怡[1] 田凤洁[1] 仇玉兰[1] 

机构地区：[1]山西医科大学公共卫生学院卫生毒理学教研室,山西太原030001

出　　处：《中国职业医学》2013年第3期204-207,共4页China Occupational Medicine

基　　金：中国博士后科学基金(20100471583);山西医科大学博士后科研启动项目;科技创新基金(01201004)

摘　　要：目的研究氯乙烯(VCM)对大鼠肝细胞P21WAF1/CIP1和P53蛋白表达的影响。方法 64只无特定病原体级SD大鼠(雌雄各半)随机分为低、中、高3个剂量组和1个对照组,采用腹腔注射染毒,低、中、高剂量组分别以5、25、125mg/kg剂量VCM气体腹腔注射染毒,对照组注射同中剂量组相同体积的清洁空气。每周3次,持续12周。染毒6、12周时每组分别随机处死8只大鼠(雌雄各半),光镜下观察染毒大鼠肝组织病理改变,免疫印迹法检测肝细胞中P21WAF1/CIP1和P53蛋白的表达。结果 VCM染毒6周时,各剂量组大鼠肝细胞P21WAF1/CIP1蛋白表达量均较对照组降低,高剂量组P53蛋白表达量较对照组增加,差异均有统计学意义(P<0.05或P<0.001)。VCM染毒12周时,高剂量组大鼠肝细胞P21WAF1/CIP1蛋白表达量高于对照组,差异有统计学意义(P<0.05)。各剂量组染毒12周和6周比较,P21WAF1/CIP1蛋白表达量均增高,差异均有统计学意义(P<0.05或P<0.001)。组织病理学检查发现VCM染毒12周时,肝细胞有气球样变,汇管区变大,纤维化等改变。结论 VCM可导致大鼠肝细胞P21WAF1/CIP1和P53蛋白表达改变。Objective To investigate the effect of vinyl chloride monomer（VCM） on the expression of liver cell cycle related proteins（P21WAF1/CIP1 and P53） of rats.Methods Sixty-four specific pathogen free male SD rats were randomly divided into 4 groups including a low-,a medium-,a high-concentration groups and a control group,with 16 rats per group.The 3 concentration groups were administrated VCM at the doses of 5,25,125 mg/kg body weight and the control group was administrated clean air with the same volume of the medium concentration group through intraperitoneal injection 3 times a week for 12 weeks.Eight rats in each groups were randomly killed at the end of 6 and 12 weeks（half male and half female）.The histopathological alterations of rat livers were observed under microscope after HE stains.Western blot was used for detecting protein expression.Results At the end of week 6,the expression of P21WAF1/CIP1 protein of rat liver cells in all of the concentration groups increased（P ＆lt;0.05 or P ＆lt;0.001）,while the expression of P53 protein of the high concentration group increased（P ＆lt;0.05）,compared with those of the control group.After a 12-week-long exposure to VCM,the expression of P21WAF1/CIP1 protein of rat liver cells in high concentration group were higher than that of the control（P ＆lt; 0.05）.Compared with the result of week 6,P21WAF1/CIP1 protein in week 12 were increased in all of the concentration groups（P ＆lt; 0.05 or P ＆lt; 0.001）.Histopathological examination revealed that hepatocyte ballooning degeneration,larger portal area,fibrosis and other pathological changes were observed in VCM exposure groups.Conclusion VCM can induce liver cells P21WAF1/CIP1 and P53 protein expression changed.

关 键 词：氯乙烯 P53蛋白 P21WAF1 CIP1蛋白 蛋白印迹 

分 类 号：R114[医药卫生—卫生毒理学] R135[医药卫生—公共卫生与预防医学]