增殖细胞核抗原在小鼠酒精性肝损伤中的表达及意义

Significance of expression of proliferating cell nuclear antigen in alcohol-induced liver injury in mice

目的:研究酒精诱导的小鼠肝损伤过程中肝脏增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达变化.方法:将100只健康清洁♂小鼠随机分为对照组(n=40)和模型组(n=60),模型组小鼠每日给予56%的红星二锅头(10 m L/kg)灌胃,对照组每日给予等体积的蒸馏水灌胃.分别于第1、2、3、4周将两组小鼠全部处死,并在各时间点取小鼠肝脏做苏木精-伊红(HE)染色并测定血清中ALT酶活力,以检测小鼠酒精性肝损伤程度.剩余肝脏通过蛋白印迹法用以检测小鼠肝脏增殖细胞核抗原的表达情况.应用SSPS16.0对实验数据进行ANOVA显著性分析和Duncan's test.结果:酒精灌胃第1周,病理HE染色显示肝细胞轻度损伤,ALT酶活力显著上升,小鼠肝脏中的PCNA的表达量相比正常小鼠显著下降(P<0.05);第2周,病理HE染色显示肝细胞出现明显的水肿和大量的炎细胞浸润,ALT酶活力高于正常,PCNA的表达量达到了最低值(P<0.01);第3周,病理HE染色显示中央静脉周围的肝细胞脂肪变性,门管区周围肝细胞水样变,ALT酶活力下降,PCNA的表达量显著上升,但仍低于正常小鼠肝脏PCNA的表达量(P<0.05).

AIM：To detect the expression of proliferating cell nuclear antigen（PCNA） in alcoholinduced liver injury in mice and to analyze its significance.METHODS：One hundred male mice were randomly divided into two groups：a model group（n=60） and a control group（n=40）.Mice were intragastrically given 56%Red Star Erguotou（model group） or equal volume of distilled water（control group） each day.Mice in each group were sacrificed at the 1st,2nd,3rd and4 th wk.The extent of alcoholic hepatic injury at each point was assessed by hematoxylin-eosin（HE） staining and determination of serum ALT.PCNA expression was detected by Western blot.RESULTS：At the first week,hepatic cells were injured mildly.The activity of ALT was increased.The expression of PCNA was decreased dramatically（P〈0.05） compared with normal mice.At the second week,liver cell swelling,inflammatory cell infiltration and other pathological changes were visible.The level of ALT was above normal.The expression of PCNA reached the minimum（P〈0.01）.At the third week,liver steatosis and hydropic degeneration were observed around the central vein and interlobular veins by optical microscopy and the activity of ALT was decreased.The expression of PCNA was increased dramatically but was lower than that in normal mice（P〈0.05）.CONCLUSION：The expression of PCNA increases in early period and then decreases during the process of hepatic injury induced by alcohol,which implies that hepatocellular injury and repair may be associated with the expression change of PCNA.