罗格列酮对脓毒症大鼠急性肺损伤保护作用的研究

摘要

Objective To investigate the protective effect of rosiglitazone on acute lung injury(ALI) in rats with sepsis and to explore the possible mechanism.Methods Fifty-four healthy male rats were randomly divided into three groups: control group(group C),acute lung injury of sepsis group(group L),rosiglitazone treatment group(group T).The acute lung injury model of sepsis was established by intraperitioneal injection of 10 mg/kg LPS.The levels of serum TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay(ELISA) 3 h,6 h,12 h after injection of endotoxin.The lung tissue was stained with hematoxylin and eosin(HE) and observed under light microscopy.The lung wet to dry weight ratio was measured,and the expression of HO-1 protein was detected by western blot.Results Compared with group C,W/D of lung tissue in group L and group T was significantly higher at each time point.Compared with group L,W/D of lung tissue in T group was significantly lower 6 h and 12 h after injection of LPS.The concentration of TNF-α and IL-6 in group L reached the peak 3 h after injection of LPS,then decreased with time.Compared with group C,serum levels of TNF-α and IL-6 in group L were significantly higher than those in group C at each time point.Compared with group L,levels of TNF-α and IL-6 in group T were significantly lower at each time point.Compared with group L,the expression of HO-1 protein in group T was significantly higher,and increased more significantly with time.Compared with group L,the pathological changes of lung tissue in group T were significantly reduced at each time point.Conclusions Our study demonstrates that pretreatment with rosiglitazone may protect against acute lung injury in septic rats through increasing the level of HO-1 protein in lung tissue and alleviating inflammatory response in sepsis rats.%目的 探讨罗格列酮对脓毒症大鼠急性肺损伤的保护作用及其机制.方法 按随机数字法,将54只健康清洁级雄性大鼠,随机分为3组,分别为对照组(C组),脓毒症急性肺损伤模型组(L组),罗格列酮治疗组(T组).采用腹腔注射内毒素脂多糖(LPS)的方法建立脓毒症急性肺损伤模型,分别于注射LPS后3 h、6 h、12 h进行心脏取血.用酶联免疫吸附试验(ELISA)测定大鼠血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平,取肺组织做HE染色,观察肺组织光镜下的病理学改变,测肺湿/干重比值(W/D),并采用western-blot法检测肺组织血红素加氧酶(HO-1)蛋白的表达.结果 与C组相比,L组和T组各时间点大鼠肺的W/D比值显著增加(P均<0.01);与L组比较,T组6、12 h时W/D显著降低(P<0.01).与C组比较,L组与T组各时间点血清TNF-α、IL-6水平显著升高(P均<0.05);与L组比较,T组各时间点血清TNF-α、IL-6水平显著降低(P<0.01或P<0.05).与C组相比,L组6、12 h时HO-1蛋白表达显著增高(P<0.01);与L组比较,T组各时间点HO-1蛋白表达显著增高(P<0.01).结论 预先加入罗格列酮可以对脓毒症大鼠急性肺损伤起保护作用,其机制可能与提高肺组织HO-1蛋白表达,减轻脓毒症大鼠的炎症反应有关.