TLR4及其信号通路在阻塞性黄疸肝脏损伤中的作用研究  

The role of TLR4 signaling pathway in obstructive jaundice liver injury

作　　者：周才进[1] 陈明[1] 邱志东[1] 姚关兵 徐浩[1] 

机构地区：[1]广东医学院附属医院肝胆外科,广东湛江524001 [2]云南省大理市大理州人民医院普外科,671000

出　　处：《广东医学》2011年第9期1104-1107,共4页Guangdong Medical Journal

基　　金：广东省科技计划项目(编号:83040);广东医学院青年基金项目(编号:Q2007035)

摘　　要：目的探讨TLR4及其信号通路在阻塞性黄疸中引起肝脏损伤的作用机制。方法将60只SD大鼠(雌雄各半)随机分为阻塞性黄疸+多粘菌素B组(OJ+PMB组,n=15)、阻塞性黄疸组(OJ组,n=15)、假手术组(SO组,n=15)、空白对照组(CG组,n=15)。结扎胆总管建立阻塞性黄疸大鼠模型,并于术后7、14、21 d采集标本,检测血清内毒素(LPS)、谷丙转氨酶(ALT)和总胆红素(TBI)含量。常规HE染色观察肝脏病变,ELISA法检测肝脏组织中TLR4蛋白表达和NF-κB p65活性,RT-PCR检测TLR4 mRNA的表达情况。结果在同一时间点,OJ+PMB组、OJ组与SO组、CG组比较,血清内毒素、ALT、TBI和肝组织TLR4、NF-κB p65均明显升高(P<0.01)。ALT与TLR4的变化呈明显正相关(r=0.875,P<0.01),并且肝组织病理损伤也随肝组织中TLR4升高而逐渐加重。脂多糖(LPS)与TLR4的变化呈正相关(r=0.848,P<0.01),TLR4与NF-κB p65的变化呈正相关(r=0.877,P<0.01),它们之间都存在明显的依存关系。21 d时,OJ+PMB组与OJ组比较各血清学指标下降,差异有统计学意义(P<0.01),病理损伤减轻。结论 TLR4的表达可加重阻塞性黄疸肝脏的损伤,并可经LPS—TLR4—NF-κB信号转导通路发挥其作用;PMB有拮抗内毒素,减轻肝脏损伤的作用。Objective To study the roles of TLR4 sigaling pathway in obstructive jaundice liver injury. Methods Sixty SD rats were randomly divided into Obstructive Jaundice ＋ Polymyxin B group（Group OJ＋PMB,n=15）,Obstructive Jaundice group（Group OJ,n=15）,Sham-operated group（Group SO,n=15） and Blank Control Group（Group CG,n=15）.The obstructive-jaundice rat model was established by bile duct ligation.Specimens were collected on the 7th,14th and 21st day after operation.Serum endotoxin（LPS）,alanine aminotransferase（ALT） and total bilirubin（TBI） were measured;Hepatic pathological changes were examined under the microscope in HE-stain sections,;Expression of TLR4 protein and NF-κB p65 activity were measured with ELISA;TLR4 mRNA expression was determined with RT-PCR. Results Significant elevation of endotoxin,ALT,TBI,TLR4 and NF-κB p65 was observed in both Group OJ＋PMB and Group OJ when comparing with those in Group SO and Group CG at all time points（P〈0.01）.Meanwhile,TLR4 was significantly positively correlated with ALT,LPS and NF-κB p65（r=0.875,0.848 and 0.877,respectively;P〈0.01）.Furthermore,hepatic pathological change was also positively correlated with TLR4 expression.Serum indicators were significantly reduced on 21st day in Group OJ＋PMB,compared with those in Group OJ（P〈0.01）,with alleviation in pathological injury. Conclusion Expression of TLR4 aggravates obstructive jaundice liver injury through LPS-TLR4-NF-κB pathway.PMB alleviates the liver injury against endotoxin.

关 键 词：TLR4 阻塞性黄疸 肝脏损伤 

分 类 号：R575[医药卫生—消化系统]