【摘要】 目的观察内毒素(ET)致兔感染性休克血浆中肿瘤坏死因子-a(TNF-a)、IL-6和肺组织核转录因子-κB(NF-κB)水平变化,探讨不同剂量乌司他汀对感染性休克的保护机制。方法将50只日本长耳大白兔随机分为内毒素致伤空白组(空白组),地塞米松(DXM)干预组(DXM组)及3种不同剂量乌司他汀(UTI)干预组(U1、U2、U3三个亚组)。用ET(2mg/kg)一次性静脉注射复制兔感染性休克模型,达休克标准后空白组应用0.9%氯化钠溶液2ml,DXM组用DXM(1mg/kg)、U1组用UTI(2.5×104U/kg)、U2组用UTI(5.0×104U/kg)、U3组用UTI(10.0×104U/kg)分别溶于2ml0.9%氯化钠溶液静脉注射进行干预,检测休克0h和干预后1、2、4、6、12h血浆中TNF-a、IL-6水平,观察肺组织免疫组化NF-κB的表达变化。结果5组兔达感染性休克标准时血浆中的TNF-a、IL-6水平比较,差异均无统计学意义(P>0.05),兔休克后不同干预时间点TNF-a、IL-6的水平在UTI组与空白组及DXM组比较,差异均有统计学意义(P<0.05);NF-κB在肺组织的表达空白组最高,U3组最低,差异有统计学意义(P<0.05)。TNF-a、IL-6的水平及NF-κB表达在U1、U2、U3组间差异均有统计学意义(P<0.05)。结论UTI可通过抑制NF-κB信号转导通路抑制TNF-a、IL-6的表达,剂量越大,作用越明显。更多还原

【Abstract】 Objective To observe the changes of tumor necrosis factor-α(TNF-α),and interleukin-6 (IL-6) in plasma,and the expression of nuclear factor-Kappa B (NF-κB) in the lungs in rabbits with septic shock induced by endotoxin,and to investigate the protective effect of different doses of Ulinastatin (UTI) to septic shock.Methods Totally 50 Japanese flap-eared white rabbits were randomly divided into 5 groups:Endotoxin induced septic shock blank group (group blank),Dexamethasone treated group (group DXM),(2.5×104) U/kg UTI treated groups (group U1),(5.0×104) U/kg (group U2),and (10.0×104) U/kg treated (group U3).Septic shock models of the rabbits were replicated by intravascular endotoxin injection (2mg/kg).Then 0.9% physiological saline (2.0ml),DXM(1.0ml/kg),and UTI in doses of (2.5×104) U/kg,(5.0×104) U/kg,and (10.0×104) U/kg were respectively given in 2.0ml 0.9% physiological saline by intravascular injection after the septic shock models were set up.At 0,1,2,4,6,12 hour after treatment,the levels of TNF-α and IL-6 in plasma of the rabbits were measured,and the expression of NF-κB in rabbits’ lungs was detected.Results The levels of TNF-α and IL-6 at 0 hour after the septic shock showed no significant difference among the five groups (P>0.05).However,the levels of TNF-α and IL-6 at 1,2,4,6,12 hour in three UTI groups were significantly decreased as compared with group blank and group DXM (P<0.05).The expression of NF-κB in group U3 was lowest as compared with other groups (P<0.05).The levels of TNF-α and IL-6,and the expression of NF-κB were degraded with the increasing dose of UTI (P<0.05).Conclusion UTI can inhibit NF-κB signal transduction pathways to inhibit the expression of TNF-α and IL-6,and the effect is increasing with the increase of dose.更多还原