辛伐他汀对脓毒症小鼠肺损伤的保护作用

目的观察辛伐他丁对脓毒症小鼠急性肺损伤的保护作用,并探讨其可能机制。方法采用盲肠结扎穿孔术制备脓毒症小鼠模型,将72只雄性C57BL/6小鼠随机分成3组:假手术组、脓毒症急性肺损伤组(脓毒症组)、脓毒症+辛伐他汀治疗组(治疗组)。治疗组给予辛伐他汀0.2μg/g,q12h腹腔注射1周;假手术组、脓毒症组给予等量安慰剂腹腔注射1周。分别于造模后6、12、24 h留取肺脏标本。HE染色观察肺组织病理学变化,免疫组化检测肺组织toll样受体4(Toll-like receptor 4,TLR4)蛋白的表达,ELISA测定肺组织匀浆中IL-1β及TNF-α的表达水平。结果与假手术组比较,造模后6、12、24 h,脓毒症组肺组织病理学评分、肺组织TLR4蛋白的表达,以及TNF-α、IL-1β水平明显升高(P<0.05);与脓毒症组相比,治疗组上述指标明显降低(P<0.05)。结论辛伐他汀通过抑制TLR4信号转导通路,减少其下游炎症介质TNF-α、IL-1β的释放,对脓毒症导致的急性肺损伤具有一定保护作用。

Protective effects of simvastatin on lung injury of sepsis mice

Objective To explore the protective effect of simvastatin on sepsis-induced lung injury of mice and its possible mechanisms.Methods Totally 72 male C57BL/6 rats were randomly divided into sham group,sepsis group of acute lung injury(sepsis group) and cecal ligation and puncture operation (CLP) + simvastatin (treatment group).Rat sepsis model was established by CLP.The mice in treatment group were intraperitoneally injected with simvastatin (0.2 μg/g,once per 12 hours) for a week;mice in sham group and sepsis group were given equal volume of placebo.The lung tissue specimens were gathered at 6,12 and 24 h after operation.Pathological changes of lung tissue were observed by HE staining;the contents of lung TNF-α and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA);the expression of TLR4 protein in lung tissues were detected by immunohistochemical method.Results The pathological scores of lung tissue,the expression of TLR4 protein and the levels of TNF-α and IL-1β in sepsis group were higher than those of sham group (P ＜ 0.05),and the above indexes in treatment group were lower than those of sepsis (P ＜ 0.05).Conclusion Simvastatin has certain protective effect on lung injury caused by sepsis.The effect may be mediated by the inhibition of TLR4 signal pathway by simvastatin and the consequent decrease of the generation of downstream inflammatory factors,such as TNF-αand IL-1β.