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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 VCM on P21WAF1 / CIP1 and P53 protein expression in rat hepatocytes. Methods Sixty-four SD rats without specific pathogens (male and female half) were randomly divided into three groups: low, medium and high dose groups and one control group. The rats were injected intraperitoneally with low dose, middle dose and high dose, 25,125mg / kg dose of VCM gas intraperitoneal injection of poisoning, the control group was injected with the same dose of the same volume of clean air. 3 times a week for 12 weeks. At 6 and 12 weeks after operation, 8 rats (male and female respectively) were randomly sacrificed in each group. The pathological changes of liver tissue were observed under light microscope. The expression of P21WAF1 / CIP1 and P53 protein in hepatocytes were detected by Western blotting . Results At 6 weeks after VCM exposure, the expression of P21WAF1 / CIP1 protein in hepatocytes in each dose group was lower than that in control group. The expression of P53 protein in high dose group was significantly higher than that in control group (P <0.05 or P <0.001). At 12 weeks of VCM exposure, the expression of P21WAF1 / CIP1 protein in hepatocytes of high dose group was higher than that in control group (P <0.05). The expression of P21WAF1 / CIP1 protein in each dose group was significantly higher at 12 weeks and 6 weeks (all P <0.05 or P <0.001). Histopathological examination found that VCM poisoned at 12 weeks, there are balloon-like hepatocytes, portal area larger, fibrosis and other changes. Conclusion VCM can induce the changes of P21WAF1 / CIP1 and P53 protein expression in rat hepatocytes.