内皮抑制素对脓毒症小鼠急性肺损伤的保护作用

[目的]研究内皮抑制素(Endostatin,ES)对脓毒症小鼠急性肺损伤的保护作用及其可能机制.[方法]雄性昆明小鼠(20~22g)150只随机分为假手术组、脓毒症模型组、内皮抑制素干预组,通过盲肠结扎穿孔(Cecal ligation and puncture,CLP)建立脓毒症模型.术后用内皮抑制素(2mg/kg,ip)干预,假手术组及模型组于同时间点给予等量生理盐水.在术后6h、12h留取标本,检测血清肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、血管内皮生长因子(VEGF)水平,同时行肺组织微血管渗漏实验、测肺湿干重比值(W/D),取部分肺组织进行组织病理学分析,并检测肺组织p38MAPK信号通路活化情况.[结果]与脓毒症模型组比较,内皮抑制素能提高脓毒症CLP模型存活率,降低血清TNF-α、IL-6、VEGFc水平,减轻肺组织的微血管渗漏、湿干重比和病理改变,同时抑制脓毒症CLP模型诱导的肺组织p38MAPK的磷酸化.[结论]内皮抑制素对脓毒症小鼠急性肺损伤具有保护作用,其机制可能与内皮抑制素能抑制过度的炎症反应、改善血管通透性及调节p38MAPK信号通路有关.

Protective Effect of Endostatin on Acute Lung Injury of Septic Mice

[Objective]To investigate the protective effect of endostatin on acute lung injury in septic mice and to explore its mechanisms behind these protective effects.[Methods]One hundred and fifty male(n =150)Kun-ming mice were randomly divided into the following groups:sham,septic model and endostatin treatment groups. The septic model was established by cecal ligation and puncture(CLP).Mice in the treatment group were adminis-trated endostatin(2mg/kg,ip)after the operation while those in the sham and septic model group were treated with equivalent amount of saline instead.Survival rates were observed for up to 3 days.The effects of endostatin on the expression of TNF-α,IL-6 and VEGF in the serum were assessed.In addition,we examined the effects of en-dostatin on Evans blue leakage,wet to dry weight ratio,histology and the phosphorylation of p38 MAPK proteins in lung tissues of septic mice.[Results]We found that endostatin increased the survival of septic mice and reduce the Evans blue leakage of lung tissues,lung wet to dry weight ratio and morphologic changes.In addition,en-dostatin reduced serum TNF-α,IL-6 and VEGF-C levels in septic mice and inhibit phosphorylation of p38 in lung tissues of septic mice.[Conclusions]Endostatin can inhibit inflammation and improve vasopermeability and regu-late the p38 MAPK signaling pathway in lung and exert protective effect on acute lung injury of septic mice.