中文摘要：

目的通过比较两种不同的补体干预方式对脂多糖（LPS）致大鼠急性肺损伤（ALI）的保护作用,进一步认识补体在LPS致ALI中的作用,并探讨补体不同成分在ALI中的作用。方法造模前将抗补体蛋白眼镜蛇毒因子（CVF）和Atrase A分别给予对应组别的大鼠,抑制补体。通过大鼠尾静脉注射LPS（5 mg.kg-1）,造成ALI模型。在给予LPS后1、6、12 h采集标本,分别测定血清补体溶血活性、肺含水量、肺组织匀浆髓过氧化物酶（MPO）活性,取支气管肺泡灌洗液（BALF）测定细胞数、蛋白含量以及TNF-α和P-selectin的含量,取肺组织行病理切片检查。通过对实验结果的分析比较,评价两种抗补体蛋白对LPS致大鼠ALI的保护作用。结果在LPS致ALI的早期伴随有明显的血清补体活性下降。模型组的血清补体活性在给予LPS后的1 h内下降了47%。采用Atrase A抑制了50%补体活性的实验组其MPO、TNF-α、P-selectin水平未上调。完全去除补体活性的CVF组其MPO活力在1 h时与正常对照组相当,在6、12 h时则上升至与模型组相当,而TNF-α和P-selectin水平则介于模型组和正常组之间。病理切片检查表明两种抗补体蛋白均能有效减轻肺组织病理损伤,其中Atrase A明显优于CVF。结论补体明确参与了LPS致ALI的病理过程。采用抗补体干预能减轻ALI炎症和相关病理损伤,但两种抗补体蛋白的保护作用有明显区别。采用CVF完全去除补体C3、C5-C9仅在ALI早期有明显的保护作用,而仅部分抑制了补体活性的Atrase A则明显优于CVF,提示Atrase A作用的补体成分可能在ALI中具有重要作用。

英文摘要：

Aim To investigate the possible roles that complement plays in lipopolysaccharide（LPS）-induced acute lung injury（ALI） by employing two kinds of anticomplementary proteins to inhibit complement in rats.Methods ALI in rats was induced by LPS administration via i.v.injection.The anticomplementary protein Atrase A or cobra venom factor（CVF） was injected to rats prior to the administration of LPS.The total cell count,protein concentration and levels of TNF-α and P-selectin in bronchoaleolar lavage fluid（BALF）,the water content,myeloperoxidase activity and pathological changes in lung tissue,and serum complement activity were measured at 1,6,and 12 h after LPS administration.Then the protective effects of Atrase A and CVF on ALI were evaluated.Results Serum complement activity in rats dropped significantly after exposure to LPS.Complement activity of model group decreased 47% in 1h after LPS exposure compared with normal group.Myeloperoxidase activity and the levels of TNF-α and P-selectin nearly didn＇t increase in the group in which 50% complement activity was inhibited by Atrase A.In CVF group in which complement activity was completely abrogated,myeloperoxidase activity showed no increase within 1 h after LPS exposure,but it increased the same as that of model group at 6,12 h.And TNF-α and P-selectin in this group arrived at middle levels between model and normal groups.Histological examination revealed that both anticomplementary proteins significantly attenuated lung pathology.However,Atrase A was much more effective than CVF.Conclusions Complement is highly relevant to ALI induced by LPS.Complement intervention attenuates lung inflammation and pathology.But the intervention by the anticomplementary proteins shows significant difference.Abrogation of the complement alternative pathway（C3 and C5-C9） by CVF attenuates lung inflammation and pathology only in the early process of ALI.Atrase A partially inhibits complement activity in rats,but it is significantly more effective than CVF in ALI,