硫普罗宁对酒精性脂肪肝大鼠肝组织细胞色素P_(450)2E1表达的影响

目的:探讨硫普罗宁对大鼠酒精性脂肪肝细胞色素P4502E1(CYP2E1)表达的影响。方法:取Wistar大鼠30只随机分为3组:A组(空白对照组)、B组(模型组)、C组(硫普罗宁组)。B组和C组大鼠均以50%乙醇灌胃进行酒精性脂肪肝的造模,C组大鼠在造模后1h灌胃给予硫普罗宁(0.15g.kg-1.d-1),连续5周后,处死所有大鼠,分别检测血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的含量;逆转录聚合酶链反应(RT-PCR)检测CYP2E1表达水平;观察肝组织病理。结果:与A组比较,B组AST、ALT、CYP2E1水平均明显升高(P<0.01);与B组比较,C组上述指标均明显降低(P<0.01或P<0.05);病理组织观察发现C组肝脏脂肪变性程度明显轻于B组。结论:硫普罗宁可能通过降低CYP2E1在肝脏中的表达而具有防治酒精性脂肪肝的作用。

Effect of Tiopronin on Cytochrome P450 2E1 Expression in Liver of Rats with Alcoholic Fatty Liver

OBJECTIVE： To explore the effect of tiopronin on the expression of cytochrome P4502E1 （CYP2E1） in liver of rats with alcoholic fatty liver. METHODS： 30 Wistar rats were randomly divided into 3 groups： group A （blank control group）, group B （model group） and group C （tiopronin group）. Group B and group C were given 50% alcohol intragastrically to establish alcoholic fatty liver model, while group C were intervened with tiopronin （0.15 g · kg-1 ·d-1 administered at 1 hour after alcohol administration） for 5 consecutive weeks. Then all the rats were sacrificed with AST and ALT levels in serum determined. The CYP2E1 expression was detected by RT PCR; and the pathologic changes of the liver tissues were observed. RESULTS： In group B compared with group A, serum levels of AST, ALT and CYP2E1 expression were significantly higher （P〈0.01）; compared with group B, the above indexes were markedly lower in group C （P〈0.01 or P〈0.05）; Histopathological examination shows that liver steatosis of group C was significantly abated as compared with group B. CONCLUSION： The preventive and curative effect of tiopronin on alcoholic fatty liver is possibly achieved by down - regulating CYP2E1 expression in liver.