姜黄素对急性百草枯中毒大鼠肝损伤中炎症反应的影响和机制  

Anti -inflammatory effect of curcumin on paraquat -induced liver injury in rats

作　　者：韩文文[1] 支绍册[1] 赵倩[1] 赵光举[1] 洪广亮[1] 李萌芳[1] 吴斌[1] 邱俏檬[1] 卢中秋[1] 

机构地区：[1]温州医科大学第一附属医院急诊医学中心,浙江温州325000

出　　处：《中国急救医学》2015年第1期62-67,I0005,共7页Chinese Journal of Critical Care Medicine

基　　金：浙江省中医药重点学科计划（2012-XK-A28）;浙江省医学创新学科建设计划（11-CX26）;浙江省“十二五”浙江省高校重点学科

摘　　要：目的探讨姜黄素（Curcumin，cu）对急性百草枯（Paraquat，PQ）中毒大鼠肝损伤中炎症反应的影响和机制。方法将60只清洁级SD大鼠随机分为4组：正常对照组（NS组，n=15），姜黄素对照组（CU组，n=15），百草枯中毒组（PQ组，n=15），姜黄素干预组（PQ＋CU组，n=15）。各组大鼠处理后第1、3、7天麻醉处死，并留取肝组织和血标本。光镜下观察各组肝组织病理变化情况，化学比色法检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）水平的变化，逆转录-聚合酶链式反应（RT—PCR）法检测转录因子TNF-仪、IL-113mRNA表达情况，双抗夹心酶联免疫吸附法（ELISA）检测TNF—α、IL-1β蛋白表达情况，Westernblot检测NF—κB蛋白表达情况。结果光镜下，PQ组大鼠肝组织损伤严重，PQ＋CU组大鼠肝组织损伤程度较PQ组有所减轻。cu组与NS组各测定指标比较差异无统计学意义（P〉0．05）。与NS组比较，PQ组ALT、AST、TBIL水平明显升高，ALT、AST在第3天达到峰值，TBIL在第1、3、7天持续升高（均尸〈0．05）；与PQ组比较，PQ＋CU组在第1、3、7天ALT、AST、TBIL水平明显降低（均P〈0．05）。与NS组比较，PQ组在第1、3、7天TNF—αmRNA、IL-1βmRNA和蛋白表达量明显升高（均P〈0．05）；与PQ组比较，PQ＋CU组TNF—αmRNA、IL-1βmRNA表达量明显降低（P〈0．05），PQ＋CU组肝组织TNF-α、IL-1β明显降低（P〈0．05）。与NS组比较，PQ组在第1、3、7天NF—κB蛋白表达量明显升高（均P〈0．05）；与PQ组比较，PQ＋CU组在第1、3、7天NF—κB蛋白表达量明显降低（均P〈0．05）。结论炎症反应是参与急性百草枯中毒肝损伤的重要机制之-，姜黄素通过抑制肝组织NF—κB炎症通路活化，使下游炎症因子TNF—κ、IL-1β水平降低，减轻百草枯中毒大鼠肝损伤的炎症反应，对急性百草枯中毒大鼠肝损伤有-定的保护[ Abstract] Objective To investigate the anti -inflammatory effect of curcumin on paraquat- induced liver injury in rats and the underlying mechanisms. Methods Sixty Sprague - Dawley male rats of clean grade were randomly divided into four groups： the normal control group （NS group, n = 15 ）, curcumin control group （CU group, n = 15）, paraquat poisoning group （PQ group, n = 15 ）, curcumin intervention group （ PQ ± CU group, n = 15 ）. After PQ or NS administration, all rats were anesthetized and sacrificed on days 1, 3, 7, and their liver tissues and blood samples were collected. Pathological changes of liver tissues were observed by light microscopy. We assessed the level of alanine aminotransferase （ALT）, aspartate transaminase （AST）, total bilirubin （TBIL） in the serum by chemical colorimetric method. The expression of tumor necrosis factor - （TNF - α ） mRNA, interleukin- 1 （IL - 1β） mRNA was measured by reverse transcription - polymerase chain （RT - PCR）, and the expression of TNF- α, IL -1β protein in the liver tissue was measured by double antibody sandwich enzyme - linked immunosorbent assay （ELISA）. The expression of NF - κB protein was measured by Western blotting. Results In comparison with NS group, the liver tissues of PQ group were damaged more severe, while histopathological lesions observed in PQ ± CU group were milder significantly. There were no significant changes when compared with NS group and CU group （P 〉 0. 05 ）. The levels of ALT, AST, TBIL in the serum in PQ group were dramatically higher than those in NS group on days 1,3,7 （P 〈 0.05 ）, and ALT, AST levels reached peak on the third day. Compared with the PQ group, the levels of ALT, AST, TBIL in the serum in PQ ± CU group on days 1, 3 and 7 were obviously decreased （ P 〈 0.05 ）. Compared with the NS group, the expression of TNF - α, IL - 1β mRNA and protein, and the expression of NF - κB protein, were significantly increased in PQ group on days 1, 3, 7 （allP〈0.

关 键 词：百草枯 肝损伤 姜黄素 核因子-κB(NF—κB) 炎症 

分 类 号：R595.4[医药卫生—内科学]