杀菌-通透性增加蛋白对脓毒症大鼠肝组织致炎与抗炎细胞因子表达的影响

Effect of recombinant bactericidal-permeability increasing protein on hepatic expression of pro-inflammatory cytokine and anti-inflammatory cytokine in septic rats

目的 :探讨杀菌通透性增加蛋白 (BPI)对脓毒症大鼠肝组织致炎与抗炎细胞因子表达的影响。方法 :采用大鼠盲肠结扎穿孔 (CL P)致脓毒症模型 ,动物随机分为正常对照组、脓毒症组和 BPI治疗组。分别于 CL P后 12和 2 4小时处死动物 ,检测肝组织肿瘤坏死因子 α(TNFα)、白介素 10 (IL 10 ) m RNA及其蛋白表达以及肝功能指标的改变。结果 :脓毒症动物肝组织 TNFα及 IL 10基因和蛋白表达均显著升高(P<0 .0 5或 P<0 .0 1) ,其中 CL P后 12小时组织 TNFα蛋白水平升高幅度明显大于 IL 10的改变。 BPI治疗 12小时组 TNFα基因及蛋白均显著下降 (P<0 .0 5或 P<0 .0 1) ,而 IL 10则不同程度地升高 ;同时 ,治疗组 12小时肝功能指标亦明显改善。结论 :脓毒症早期应用 BPI治疗可明显抑制肝组织 TNFα等致炎细胞因子表达 ,并上调局部组织 IL 10等抗炎细胞因子的产生 。

Objective:To evaluate the effect of recombinant bactericidalpermeability increasing protein (BPI) on proinflammatory cytokine and antiinflammatory cytokine expression in the liver of septic rats.Methods:Wistar rats were subjected to sepsis induced by cecal ligation and puncture (CLP),and animals were randomly divided into normal controls ( n =10),sepsis group ( n =20),as well as BPItreated group ( n =20).Animals were sacrificed at 12 and 24 hours after CLP.The tumor necrosis factorα(TNFα) and interleukin10 (IL10) protein levels and their mRNA expressions in liver tissue were measured at various intervals. Also, the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) were determined at the same time.Results:After CLP,liver tissue TNFα and IL10 mRNA and protein expression levels were markedly increased ( P <0 05 or P <0 01),particularly in local TNFα protein expression at 12 hours after sepsis.Treatment with BPI,however,liver tissue TNFα gene as well as protein levels were significantly reduced, tissue IL10 expression levels were markedly increased ( P <0 05).Meanwhile,the levels of ALT and AST in septic group were much lower than that in BPItreated group.Conclusions:Early treatment with BPI can inhibit proinflammatory cytokine expression,while upregulate antiinflammatory cytokine formation in liver,thereby regulating the balance of local inflammatory response and protecting against acute liver injury in rats following CLPinduced sepsis.