磷酸化的信号转导及转录激活因子3在小鼠乙醇性肝损伤过程中的作用

Function of phosphorylated signal transducer and activator of transcription 3 in alcoholic liver injury of mice

目的研究磷酸化的信号转导及转录激活因子3(p-STAT3)在小鼠乙醇性肝损伤过程中的作用。方法按照体重将小鼠随机分成5组,每组10只:正常组和实验1组、实验2组、实验3组、实验4组。正常组不做任何处理,实验1,2,3,4组于每天不间断用56度北京红星二锅头进行灌胃,1天/次,每次14m L·kg^(-1),制备小鼠乙醇肝损伤模型。分别于灌胃后1,2,3,4周,摘出眼球取血。根据试剂盒方法测定血清谷草转氨酶(AST)的含量。用免疫印迹法检测小鼠肝中蛋白的p-STAT3表达量。结果正常组、实验1组、实验2组、实验3组与实验4组的血清AST水平分别为(112±22),(126±24),(967±30),(1010±35),(206±23)U·L^(-1);在乙醇灌胃1,4周后,实验1组和实验4组与正常组的AST水平相比,差异均无统计学意义(均P>0.05);在乙醇灌胃2,3周后,实验2组和实验3组与正常组相比,差异均有统计学意义(均P<0.01)。正常组、实验1组、实验2组、实验3组与实验4组的p-STAT3相对表达量分别为(0.52±0.11),(3.21±0.33),(1.12±0.21),(1.51±0.23),(2.13±0.26)AU。实验1组和实验4组与正常组比较,差异均有统计学意义(均P<0.01);实验2组和实验3组与正常组比较,差异均有统计学意义(均P<0.05)。结论p-STAT3可能参与小鼠肝损伤早期阶段的急性期反应,参与并促进肝细胞损伤;在后期,可能参与肝细胞再生、修复以及对肝细胞细胞凋亡的抑制。

Objective To research the role of phosphorylated signal transducer and activator of transcription 3（ p-STAT3） in the pathogenesis of alcoholic liver injury in mice. Methods Healthy and mature male mice were reared normally. They were divided at random into 5 groups,namely the normal group（ n = 10）, the experimental^-1 group（ n = 10）,the experimental-2 group（ n = 10）,the experimental-3 group（ n = 10）,the experimental-4 group（ n = 10）. The normal group was not treated. The mouse in experimental^-1 group,experimental-2 group,experimental-3 group,experimental-4 group were given uninterruptedly 56 degree Beijing Red Star Erguotou by intragastric administration（ 14 m L·kg^-1） for preparation of alcohol liver injury in mice. At the first week,the second week,the third week and the fourth week,respectively,the blood of mice was taken directly by eyeball enucleation. The serum levels of aspartate aminotransferase（ AST） was measuredwith a aspartate aminotransferase assay kit. The expression levels of p-STAT3 in liver of mice was measured by Western blot. Results The serum levels of AST in normal group,experimental^-1 group,experimental-2 group,experimental-3 group,experimental-4 group were（ 112 ± 22）,（ 126 ± 24）,（ 967 ± 30）,（ 1010 ± 35）,（ 206 ± 23） U·L^-1; comparison between experimental-1group,experimental-4 group and normal group,the difference were without significantly（ all P〈0. 05）; comparison between experimental-2 group,experimental-3 group and normal group,the difference had significantly（ all P〈0. 01）. The expression levels of p-STAT3 in the 5 groups were（ 0. 52 ± 0. 11）,（ 3. 21 ± 0. 33）,（ 1. 12 ± 0. 21）,（ 1. 51 ± 0. 23）,（ 2. 13 ± 0. 26） AU; comparison between experimental-1 group,experimental-4 group and normal group,the difference had significantly（ all P〈0. 01）; comparison between experimental-2 group,experimental-3 group and normal group,the difference had significantly（ all P〈0. 05）. Conclusion P-STAT3 may be involved in the acute phase response in the early stage of liver injury in mice,and participate in and promote hepatocyte injury. In the later stage,it may be beneficial to the regeneration,repair and inhibition of hepatocyte apoptosis.