SOD及NF-κB在梗阻性黄疸大鼠肝脏损伤中的作用

Roles of SOD and NF-κB in Liver Injury of Obstructive Jaundice in Rats

目的:检测超氧化物歧化酶(superoxide dismutase,SOD)活力及核因子-κB(nuclear factor-κB,NF-κB)在梗阻性黄疸大鼠肝脏中的表达,探讨其在梗阻性黄疸大鼠肝脏损害中的作用。方法:采用胆总管结扎法构建梗阻性黄疸大鼠模型,检测血清总胆红素(totalbilirubin,TB)、直接胆红素(direct bilirubin,DB)和谷丙转氨酶(alanine aminotransferase,ALT),以及肝脏组织行HE病理切片检查鉴定梗阻性黄疸大鼠模型。肝脏组织匀浆后检测组织中总SOD和CuZn-SOD活力,以免疫组织化学方法检测NF-κB在肝脏中的表达。结果:胆道结扎(Bile duct ligation,BDL)组血清TB、DB及ALT明显增高(P<0.01);胆道结扎组肝组织中总SOD和CuZn-SOD活力较假手术组明显减低(P<0.01)。胆道结扎组NF-κBp65蛋白激活并出现核移位,19d组较7d组更加显著。结论:脂质过氧化是梗阻性黄疸器官损伤的最重要的机制之一,而SOD活力的降低及NF-κB的激活,在梗阻性黄疸肝脏过氧化损害中具有重要意义。

Objective ： To determine the activities of SOD and the expression of nuclear factor-κB（NF-κ B） in rats with obstructive jaundice induced by bile duct ligation（BDL）, and elucidate the mechanisms of hepatic injury due to obstructive jaundice. Methods ： The animal model of obstructive jaundice in rats were made to be bile duct ligation. All rats were sacrificed on the 7th day and 19th day after BDL. The blood and liver tissue samples were obtained. Total bilirubin（TB）, direct bilirubin（DB）, alanine aminotransferase（ALT） in serum were detected and liver tissue HE pathology section were evaluated. SOD enzyme activity was detected by SOD kit. The detection of activation of NF-KB was performed by an immunohistochemical method. Results ： In BDL animals serum, TB, DB, and ALT significantly increased compared with the sham group （P〈0.01）. By HE pathology section, we observed that in the BDL group, in liver significant damage signs occurred , and the change on 19th day after BDL was more obvious. The activities of normal SOD and CuZn-SOD decreased compared to the sham group（P〈0.01）, and the decrease on 19th day after BDL was more significant. In BDL group, NF-κBp65 activation and nuclear displacement response, on 19th day after BDL, were more significant. Conclusion ： Oxidative stress probably plays an important role in liver injury induced by obstructive jaundice. Down-regulated expression of SOD and NF-κBp65 activation may be the important molecule mechanism in liver damage of obstructive jaundice.