高密度脂蛋白对腹腔感染败血症小鼠保护作用的实验研究

Experimental study of the protective effects of high-density lipoprotein on sepsis mice

目的探讨高密度脂蛋白对败血症的保护作用及其机制。方法采用盲肠结扎并穿孔(cecal ligation and puncture,CLP)法复制败血症模型。60只健康昆明小鼠随机分为对照组(假手术组)、CLP组和高密度脂蛋白组,每组20只,记录3组小鼠48h总体生存率和平均生存时间。另取36只小鼠随机分为对照组、CLP组和高密度脂蛋白组,每组12只。其中每组6只于模型制备成功后2h处死动物取血,采用酶联免疫吸附法检测血浆肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)的浓度。每组小鼠6只于模型制备成功后12h取肝、肺组织进行光镜和电镜学检查。结果48h内对照组、CLP组和高密度脂蛋白组小鼠生存率分别为100%、20%和56.7%,差异具有显著性(P<0.05)。光镜下CLP组肝细胞肿胀,肝血窦扩张。电镜下可见CLP组肝细胞凋亡,细胞器明显破坏。高密度脂蛋白组肝组织病理改变较CLP组明显减轻。并且,CLP组血浆TNF-α的浓度较对照组明显升高。而高密度脂蛋白组血浆TNF-α的浓度与CLP组相比,明显降低,差异具有显著性(P<0.05)。结论高密度脂蛋白可以改善腹腔感染败血症小鼠肝脏、肺脏的病理组织学改变,降低严重感染导致的机体促炎性细胞因子水平的,提高小鼠总体生存率。

Objective To investigate the protective effects of high-density lipoprotein（HDL） on sepsis.Methods Sixty healthy female mice were randomly divided into 3 groups and each group 20 mice ：（1）Control group received sham operation;（2）CLP group received a cecal ligation and puncture（CLP）;（3） HDL group were intravenous injected with HDL after performing CLP.The mortality mice were observed during 48 hours.Thirty six mice were randomly divided into 3 groups,each group 12 mice.The content of tumor necrosis factor-alpha（TNF-α） in serum was measured by ELISA.The liver tissues and lung tissues were collected after operation and histopathological examinations were performed.Results The survival rates of CLP group were significantly decreased than that of control group（P＆lt;0.05）.Compared with control group,the serum content of TNF-α in CLP group was significantly increased（P＆lt;0.05）.While HDL could significantly attenuate TNF-α content in serum and increase the survival rates（P＆lt;0.05）.Compared with CLP group,there were obvious histopathological changes in hepatic tissues and lung tissues in HDL group.Conclusion HDL can significantly redule the production of pro-inflammatory cytokine,alleviate the inflammation of liver and lung and increase the survival rates of sepsis mice.HDL might have a potential protective effect on sepsis mice.