细胞色素P4502E1在小鼠乙醇性肝损伤过程中的表达及意义

Expression and significance of cytochrome P4502E1 of alcoholic liver injury in mice

目的研究细胞色素P4502E1(CYP2E1)在乙醇诱导的小鼠肝损伤过程中的动态变化及其意义。方法按照体重将雄性小鼠随机分为模型组40只和对照组10只,用56°红星二锅头以10 mL·kg^(-1)的剂量持续灌胃4周,建立小鼠乙醇性肝损伤模型。分别于建模前(对照组)和给予二锅头1,2,3,4周,各取10只小鼠,眼球取血,测定血清谷草转氨酶(AST)的活性;颈椎脱臼处死小鼠,取小鼠肝,以免疫组化SP法检测CYP2E1阳性细胞数量。结果模型组小鼠肝AST的活性在1,2,3,4周分别为(126±24),(967±30),(1010±35),(206±23)U·L^(-1)。与对照组的(112±22)U·L^(-1)相比,模型组小鼠肝AST的活性在第1,2,3周持续升高(第3周达到高峰),差异均有统计学意义(均P<0.01);于第4周下降,但仍高于对照组,差异有统计学意义(P<0.05)。小鼠肝组织中每平方毫米CYP2E1阳性细胞数量(cell·mm^(-2))在这4周分别为(3.2±0.8),(8.4±1.1),(13.2±1.3),(4.6±0.8)cell·mm^(-2),与对照组的(2.8±0.5)cell·mm^(-2)相比,第1,2,3周显著增高,差异均有统计学意义(均P<0.01);第4周有所下降,但仍多于正常组,差异有统计学意义(P<0.05)。结论在乙醇诱导小鼠肝损伤模型的过程中,CYP2E1的表达是先上升后下降,与血清AST酶的活力变化趋势一致。其表达的动态变化可能与肝的损伤与修复有着重要的关系。

Objective To study the dynamic changes of cytochrome P4502E1 （ CYP2E1 ） in alcohol - induced liver injury in mice and its sig- nificance. Methods Fifty male mice were randomly divided into model group （ n =40） and control group （ n = 10）. The model of alcoholic liver injury was established by continuous infusion of 56 o Ergnotou at 10 mL · kg^-1 for4 weeks. At the time ofl, 2, 3, 4 weeks,to take 10 mice, eye blood for serum aspartate aminotransferase （AST） activity determina- tion. Followed by cervical dislocation of mice, the number of CYP2E1 positive cells in mice liver were detected by immunohistochemical SP method. Results The activity of hepatic AST enzyme in model group were （126 ±24）, （967 ±30）, （1010 ±35） and （206 ±23） U · L^-1 in 1st, 2nd, 3rd and 4th weeks, respectively. Compared with the control group （112 ±22） U · L^-1, the activity of hepatic AST enzyme in the model group increased continuouslyfrom 1st to 3rd weeks and reached the peak at 3rd week with significantly （ P 〈 0. 01 ）, which was decreased at the 4th week, but still higher than the control group with significantly （P 〈0. 05）. The number of CYP2E1 positive cells per square millimeter were （3. 2 ±0. 8）, （8. 4 ± 1.1 ）, （ 13. 2 ± 1.3） ,and （4.6±0.8） cell - mm-2 in 1st, 2nd, 3rd and 4th weeks. Compared with the control group （2.8 ±0.5） cell · mm-2, the number were obviously increased in 1st, 2nd and 3rd weeks and represented statistically significant （P 〈0.01）while the number of the 4th week decreased but still with statistically significant（P 〈0. 05）. Conclusion The expression of CYP2E1 was increased first and then decreased in alcohol - induced liver injury model, which was consistent with the trend of serum AST enzyme activity. The dynamic changes in expression may be associated with damage and repair of the liver.