杀菌/通透性增加蛋白对脓毒症大鼠组织TNF-α表达的影响及意义

The effect of recombinant bactericidal/permeability increasing protein on tissue tumor necrosis factor-α expression in septic rats

目的 探讨杀菌 /通透性增加蛋白 (BPI)对脓毒症动物肝、肺肾组织肿瘤坏死因子 α (TNF -α)表达及多器官功能障碍的影响与意义。方法 采用大鼠盲肠结扎穿孔 (CLP)造成脓毒症模型。动物分为正常对照组 (10只 )、CLP组 (2 0只 )及BPI治疗组 (2 0只 )。CLP后 12h和 2 4h处死动物 ,分别检测肝、肺、肾组织TNF αmRNA表达、TNF α蛋白水平和器官功能指标。结果 CLP后 12h动物肝、肺、肾组织TNF αmRNA表达均显著增强 ,分别为伤前基础值的 2 4 6倍 (P <0 0 5 )、 2 86倍 (P <0 0 1)、 2 2 7倍 (P<0 0 1) ,同时各组织TNF α水平迅速升高 (P <0 0 1)。重组BPI治疗可不同程度地抑制肝、肺、肾组织TNF -αmRNA表达上调 (P <0 0 5 ) ,12h各组织TNF α水平显著降低 (P <0 0 5 ) ,均恢复至伤前正常范围。此外 ,BPI组动物血清丙氨酸转胺酶、肌酐水平在CLP后 12h显著低于未治疗组 ,CLP后 2 4h肺组织髓过氧化物酶活性也明显下降 (P <0 0 1)。结论 严重腹腔感染早期应用重组BPI治疗有助于下调TNF α的过量表达 ,从而抑制机体过度炎症反应 。

Objective To evaluate the effect of recombinant bactericidal/permeability increasing protein(BPI) on tissue tumor necrosis factor-α (TNF-α)expression and multiple organ dysfunction in 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),septic group( n =20),and BPI-treated group( n =20).Animals were sacrificed at 12 and 24 hours after CLP.Tissue TNF-α mRNA expression and protein levels in liver,lungs,as well as kidneys were measured at various intervals.Serum alanine aminotransferase(ALT) and creatinine(Cr) levels,and pulmonary myeloperoxidase(MPO) activities were also determined.Results TNF-α mRNA expression levels in liver,lungs,as well as kideys were markedly increased at 12 hours post-CLP,being 2 46-fold( P <0 05),2 86-fold( P <0 01),and 2 27-fold( P <0 01) of baseline values,respectively.Meanwhile,TNF-α protein levels in various tissues were significantly elevated compared to normal controls(all P <0 01).In the BPI-treated group,however,TNF-α mRNA expression in liver,lungs,and kidneys were markedly down-regulated at 12 hours( P <0 05),together with significant decreases in local TNF-α protein levels and recovery to normal range ( P <0 05).In addition,serum ALT as well as Cr levels at 12 hours,and pulmonary MPO activities at 24 hours in the septic group were much lower than those in the BPI-treated group( P <0 01).Conclusion Early treatment with BPI could markedly inhibit TNF-α synthesis and release in vital organs,thereby preventing the development of excessive inflammatory response and subsequent multiple organ dysfunction syndrome associated with CLP-induced sepsis. [