摘要
目的:探讨蜕皮甾酮(EDS)对脂多糖(LPS)所致大鼠急性肺损伤(ALI)肺组织病理学及IL-10表达的影响。方法:将健康成年雄性Wistar大鼠120只,随机分为空白对照组、ALI模型组(LPS组)和蜕皮甾酮低剂量组(LPS+EDS 20 mg/kg组)、蜕皮甾酮中剂量组(LPS+EDS 30 mg/kg组)、蜕皮甾酮高剂量组(LPS+EDS 40mg/kg组)。经腹腔注射脂多糖(8 mg/kg)复制ALI模型,蜕皮甾酮各剂量组于建模1 h后同时尾静脉注射相应剂量的蜕皮甾酮溶液;在建模后2、4、24 h处死动物,采用实时荧光定量RT-PCR检测肺组织白细胞介素-10(IL-10)mRNA表达的变化,酶联免疫吸附(ELISA)法检测血清IL-10浓度变化,检测各组肺组织湿重/干重比值(W/D)变化;建模24 h后光镜观察肺组织病理学改变,电镜观察肺泡Ⅱ型上皮细胞(AT-Ⅱ)超微结构变化。结果:与LPS组比较,EDS不同剂量治疗组在同一时间点均不同程度促进肺组织IL-10 mRNA和血清IL-10水平的升高(P<0.05)。其中EDS高剂量组(P<0.05)促进作用最明显,在各个时间点IL-10 mRNA的表达和注射LPS4 h血清IL-10水平均显著高于低剂量治疗组(P<0.05)。而在注射LPS后4和24 h,治疗组W/D均显著低于模型组(P<0.05)。光镜、电镜观察结果提示EDS治疗减轻了ALI造成的肺组织形态学改变:治疗组较模型组肺水肿程度及炎症细胞浸润程度明显减轻,AT-Ⅱ线粒体肿胀、微绒毛减少、板层小体空泡化程度减轻。结论:蜕皮甾酮对脂多糖致急性肺损伤起保护效应,这一作用可能与促进肺组织IL-10 mRNA表达、血清IL-10浓度上调有关,从而调节全身炎症反应和代偿性抗炎反应的动态平衡,抑制肺部炎症反应。
Objective：To investigate the effect of ecdysterone （EDS）on pathologic changes and expression of IL-10 in lung tissue and its mechanism during the development of acute lung injury （ALl） induced by lipopolysaccharide （LPS）in rats. Methods：One hundred and twenty male adult Wistar rats were randomized into 5 groups：normal control group, ALI group （LPS）, low dosage of EDS-treatment group （LPS＋EDS 20 mg/kg）, middle dosage of EDS-treatment group （LPS＋ EDS 30 mg/kg）, high dosage of EDS-treatment group （LPS＋ EDS 40 mg/kg）. All the rats were injected intraperitoneally with 8 mg/kg LPS, except for the normal control group. The EDS-treatment groups received intravenous injection of EDS at the doses of 20, 30, 40 mg/kg respectively, 1 hour after the administration of LPS. The blood samples and lung tissue were collected at 2, 4 and 24 hours after LPS injection. The mRNA expression of IL-10 in the lung tissues was assessed by fluorescence quantitative real-time RT-PCR, and the concentration of IL-10 in plasma was determined by ELISA at different time points. The lung wet/dry（W/D）ratio was calculated at different time points. Meanwhile, the pathological changes in lung tis-sue were observed by light microscopy, and the ultrastructural changes in lung tissue were observed by electron microscopy 24 hours after LPS injection. Results：The lung IL-10 mRNA expression levels and IL-10 levels in LPS and EDS-treatment groups were all significantly higher than those of control group （all P〈0. 05）, and they were all significantly higher in EDS-treatment group than those of LPS group （P〈0.05）. The lung IL-10 mRNA expres-sion levels at the different time points and plasma IL-10 levels 4 hours after LPS injection were also higher in LPS ＋EDS 40 mg/kg group than those in LPS＋EDS 20 mg/kg group （all P〈0.05）. The lung W/D in EDS-treat-ment groups was significantly lower than those of LPS group （P〈0.05） 4 and 24 hours after LPS injection. The pathological changes in lung induced by LPS were alleviated significantly in EDS-treatment groups as seen under light or electron microscope, with numbers of decrease in inflammatory cells and lung edema. Disappearance of su-perficial microvilli of type Ⅱ alveolar＇cells and atrophy of lamellar body were also lessened. Conclusion： Ecdyste-rone administration protects the lung against acute lung injury, especially with a dose of 40 mg/kg of in rats. The mechanism may be an increase in the expression of IL-10 mRNA and concentrations of IL-10 in plasma after ad- ministration of ecdysterone.
出处
《感染．炎症．修复》
2012年第4期207-211,F0003,共6页
Infection Inflammation Repair
基金
中国博士后基金资助项目(20100471820)
南方医科大学南方医院院长基金项目(2010B022)
关键词
蜕皮甾酮
脂多糖
肺损伤
急性
白细胞介素-10
超微结构
Ecdysterone
Lipopolysaccharide
Acute lung injury
Interleukin-10
Ultrastructure of lung
作者简介
通讯作者：吴旭，主任医师（E-mail：wuxu5888@fimmu．com）
