酒精性肝病羰基应激状态下蛋白酶体LMP7亚基表达研究

Expression of LMP7 in alcoholic liver disease under carbonyl stress

目的:分析酒精性肝病羰基应激状态下蛋白酶体活性亚基LMP7 mRNA的表达量,研究其在酒精性肝病发病机制中的作用。方法:利用酒精灌胃的方法建立大鼠酒精性肝病模型,分批于6、8、10、12周处死大鼠。采用2,4-二硝基苯肼比色法测定大鼠肝组织蛋白质羰基含量,荧光定量PCR方法测定蛋白酶体活性亚基LMP7 mRNA表达量。结果:模型各组肝组织中羰基含量均明显高于正常对照组(P<0.05),并随肝组织病理损害程度的加重而逐渐增高;LMP7亚基mRNA水平逐渐降低,并与羰基含量呈负相关。结论:酒精性肝病时组织处于羰基应激状态,蛋白酶体活性亚基LMP7基因表达下降,可能在酒精性肝病发病机制中发挥重要作用。

Objective： To evaluate the expression of proteasome LMP7mRNA in rat models of alcoholic liver disease under carbonyl stress and investigate the effect of LMP7 in the pathogenesis of alcoholic liver disease. Methods： Rat models of alcoholic liver disease were establish by the gastric perfusion method and killed at 6,8,10 and 12 weeks. Protein carbonyl contents at different stages were determined by 2, 4-Dinitrophenylhydrazine colorimetry, and expressions of mRNA for LMP7 were determined by RT-PCR. Results： Compared with the control group, contents of protein carbon- yl were much increased in the model groups in a dose-dependent manner （ P 〈 0.05）. Expressions of mRNA for LMP7 were decreased in the model groups, which negatively correlated with the protein carbonyl content. Conclusion： Hepatic tissues are under carbonyl stress in alcoholic liver disease, and the alcohol administration results in a decreased expression of LMP7, which may play a vital role in the pathogenesis of alcoholic liver disease.