眼镜蛇毒因子抑制脓毒症大鼠的炎症反应

Cobra venom factor inhibites inflammatory responses of septic rats

目的观察补体抑制剂眼镜蛇毒因子(CVF)对脓毒症大鼠血清细胞因子释放的影响及对肺组织的保护作用。方法144只清洁雄性SD大鼠(体重250～300g)随机分为A、B、C3组,每组48只。A组假手术组,B组(脓毒症组)采用盲肠结扎穿孔术(CLP)复制脓毒症大鼠模型,C组(CVF组)在盲肠结扎穿孔术前24h按50μg/kg注射CVF,A和B组给予等量生理盐水。于术后6个时间点分别采用放射免疫分析法和酶联免疫吸附法检测血清TNF-α、IL-6和IL-10水平,肺组织MPO含量及病理学改变。结果B组大鼠脓毒症反应最强,A组表现轻微;B组TNF-α及IL-6水平均明显高于A组(P<0.05,P<0.01);B组除2h点外,肺组织MPO水平显著高于A组(P<0.05,P<0.01);B组肺组织损伤最严重;C组经CVF干预后脓毒症反应及肺组织损伤较B组明显减轻,TNF-α、IL-6及MPO水平均较B组明显下降(P<0.05,P<0.01)。结论补体抑制剂CVF可减轻脓毒症大鼠的炎症反应,具有肺保护作用。

Objective To investigate the effects on release of serum cytokines and protection of lung tissues by inhibiting complement activation with cobra venom factor （CVF）. Methods One hundred and 44 SD rats （ clean, male ,250 -300 g） were randomly divided into three groups （each n = 48 ） ：group A （sham group） ; group B （sepsis group） in which sepsis was induced by cecal ligation and puncture （CLP）; group C（ CVF pretreatment）：sepsis was induced by CLP after pretreatment with CVF, rats were given a dose of 50 μg/kg CVF before operation, an equal volume of saline solution in group A and group B. MPO contents, level of TNF-α,IL-6 and IL-10 were measured at 6 hours points. Lung tissues were observed for change of histopathology. Results The manifestations of sepsis were more severe in group B than that of group A. The level of TNF-α and IL-6 was higher in group B than that of group A （ P 〈 0.05, P 〈 0. 01 ）. MPO content of lung tissues was higher in group B than that of group A （P 〈0. 05 ,P 〈0. 01 ）. Histological damage was much severe in group B than in group A. However, after injection CVF in group C, the manifestations of sepsis were much lighter and the levels of TNF-α, IL-6 and MPO were decreased obviously （P 〈0. 05 ,P 〈0. 01 ）. The histologic damage ameliorated in CVF group as compared to that of group B. Conclusion CVF alleviates the systemic inflammatory response and provide protection to lung tissue of septic rats.