急性出血坏死性胰腺炎肝损伤中TLR2/4mRNA的表达及氯喹的干预效应

目的： 研究急性出血坏死性胰腺炎（AHNP）肝损伤中Toll-样受体(TLR)2/4mRNA表达的变化及氯喹的干预效应。 方法：采用逆行胰胆管牛磺胆酸钠（TAC）注射造成大鼠AHNP肝损伤动物模型。动物分为假手术组（S组）、胰腺炎组和氯喹（CQ）治疗组。后2组于术后3，6，12 h分批剖杀，S组于术后6 h剖杀。观察血清淀粉酶、ALT和AST及肝组织NO和TNF-α的变化，RT-PCR方法检测各组不同时点肝组织TLR2和TLR4mRNA的表达。 结果：相对于S组，胰腺炎组大鼠3 h肝组织TLR2和TLR4mRNA表达开始增高，术后6～12 h肝组织TLR2和TLR4mRNA表达迅速达到峰值（P<0.05），肝损伤加重，血清淀粉酶升高，肝组织TNF-α浓度升高，NO浓度逐渐降低（P<0.05）；相对胰腺炎组，CQ治疗组TLR2/4mRNA表达降低（P<0.05），肝损伤程度减轻，血清淀粉酶降低，肝组织TNF-α浓度降低，NO浓度显著升高（P<0.05）。 结论：AHNP大鼠肝组织内TLR2和TLR4的基因表达上调；其表达增高可能在AHNP肝损伤的发生、发展中起重要作用。氯喹对大鼠AHNP过程中肝损伤可能有保护作用。

Toll-like receptor 2 and 4 gene expression in acute injury liver tissue of acute hemorrhagic necrotizing pancreatitis rats and the efficacy of intervention with Chloroquine

Abstract:Objective：To investigate the changes of Toll-like receptor 2 and 4 gene expression in acute injury liver tissue of acute hemorrhagic necrotizing pancreatitis (AHNP) rats and the efficacy of intervention with chloroquine(CQ). Methods：Seventy SD male rats were randomly divided into Sham-operated group (n=10), AHNP group (n=30) and Chloroquine-treated group (n=30). Levels of serum amylase, ALT, AST, NO and TNF-α were detected. TLR2/4mRNA expression in the livers were measured by RT-PCR. Results： Comparing to sham-operated group, TLR2/4mRNA was markedly increased at 3 hours in liver tissues in AHNP group, peaking at 6～12 hours (P<0.05 ). As liver injuries were aggravated, the levels of serum amylase, ALT, AST and TNF-α were increased and the level of NO in livers was decreased (P<0.05 ). Treatment with CQ could effectively inhibit TLR2/4mRNA expression (P<0.05), and the degree of liver injuries was decreased, and the levels of serum amylase, ALT, AST and TNF-α were decreased and the levels of NO were also markedly increased (P<0.05 ). Conclusions：The expression of TLR2/4mRNA is increased in livers in AHNP. Up-regulation of TLR2/4mRNA expression in livers may be importantly involved in the pathogenesis and development of acute liver injury in AHNP rats. CQ may have protective effect against liver injuries induced by AHNP.