辛伐他汀对脓毒血症大鼠肺损伤的保护作用

Protective effect of simvastatin on lung injury in rats with sepsis

目的 探讨辛伐他汀对脓毒血症大鼠肺损伤的保护作用及其机制。方法 选取成年雄性Wistar大鼠36只,随机分为假手术组、脓毒血症组和治疗组。建模前1周进行药物干预,其中,治疗组腹腔注射辛伐他汀0.2μg/g,每12 h 1次,连续治疗1周。假手术组和脓毒血症组腹腔注射同等剂量安慰剂。取建模24 h后的支气管肺泡灌洗液(BALF),利用蛋白定量试剂盒对总蛋白进行定量,采用酶联免疫吸附法测定脂钙蛋白2(LCN2)和肿瘤坏死因子-α(TNF-α)水平,并对多形核中性粒细胞(PMN)进行计数。取各组大鼠肺组织,采用硫代巴比妥酸(TBA)法检测丙二醛(MDA)水平,黄嘌呤氧化酶法检测超氧化物歧化酶(SOD)活性。肺湿/干重(W/D)比值评估肺水肿情况。HE染色评估肺组织病理变化。结果 与假手术组相比,脓毒血症组的支气管肺泡灌洗液中LCN2、TNF-α和总蛋白水平以及PMN计数均显著增高,肺组织SOD活性下降,MDA水平升高,W/D比值升高。与脓毒血症组相比,治疗组支气管肺泡灌洗液中LCN2、TNF-α、总蛋白水平以及PMN计数均显著降低,肺组织SOD活性增高,MDA水平降低,W/D比值下降。肺组织HE染色结果显示,脓毒血症组大鼠肺损伤明显,辛伐他汀治疗可显著改善肺损伤。结论 辛伐他汀可降低脓毒血症大鼠肺组织的炎症和氧化应激,继而减轻急性肺损伤。

Objective To observe the protective effects of simvastatin on sepsis-induced acute lung injury(ALI) in rats and to explore the underlying mechanism of the protective effects. Methods In total,36 adult,male Wistar rats were randomly divided into three groups:sham,sepsis,and treatment(n=12 each). One week before operation,the treatment group received intraperitoneal injection of 0.2 μg/g simvastatin every 12 hours,whereas the sham and sepsis groups received placebo at the same dose. Sepsis was induced by cecum ligation and puncture(CLP);however,the sham group did not undergo CLP. Bronchoalveolar lavage fluid(BALF) was collected 24 hours after modeling. The total protein level was quantified using a protein quantification kit,and lipocalin 2 and TNF-α levels were measured using ELISA. Moreover,polymorphonuclear neutrophils(PMN) were counted. Next,lung tissues were collected from rats in each group.Malondialdehyde(MDA) level was determined with the thiobarbituric acid colorimetric method,and superoxide dismutase(SOD) activity was assessed with the yellow purine oxidase method. Pulmonary edema was assessed by calculating the lung wet/dry mass ratio(W/D).Further,H&E staining was performed to evaluate the pathological changes in lung tissues. Results The sepsis group demonstrated significantly increased lipocalin 2,TNF-α,and total protein concentrations and PMN count in BALF;MDA content;and W/D ratio as well as significantly decreased pulmonary SOD activity. Compared with the sepsis group,the treatment group showed significantly decreased lipocalin 2,TNF-α,and total protein concentrations and PMN count in BALF;MDA content;and W/D ratio,but significantly increased pulmonary SOD activity. Moreover,obvious lung injuries in the sepsis group were shown to be alleviated in the simvastatin group when observed under a light microscope. Conclusion Simvastatin reduces lung inflammation and oxidative stress in septic rats,thereby alleviating ALI.