白藜芦醇对脓毒症大鼠急性肺损伤的保护作用及对巨噬细胞炎症蛋白-2、IL-10、IL-18表达的影响

Protective effect of resveratrol on rats with acute lung injury induced by sepsis in rat and its influence on expressions of macrophage inflammatory protein-2,IL-10 and IL-18

目的研究白藜芦醇(Resveratrol,Res)对脓毒症大鼠急性肺损伤(Acute lung injury,ALI)的保护作用及对ALI大鼠肺组织中巨噬细胞炎症蛋白-2(Macrophage inflammatory protein,MIP-2)、白细胞介素-10(Interleukin-10,IL-10)和白细胞介素-18(Interleukin-18,IL-18)表达的影响。方法将SD大鼠随机分为空白对照组(Con组)、假手术组(Sham组)、脓毒症组(Sep组)和白藜芦醇组(Res组)。采用盲肠结扎穿刺术(Cecal ligation and puncture,CLP)制备脓毒症相关性ALI大鼠模型,造模24 h后,Res组给予0.3 ml/100 g的Res液,Con、Sham和Sep组给予等量生理盐水,均经尾静脉注射。各组分别于0、6、12、24和48 h,取大鼠肺组织,HE染色观察病理形态学变化,计算肺湿重/干重比值(W/D);ELISA法检测各组大鼠血浆中MIP-2、IL-10和IL-18含量;Western blot法检测各组大鼠肺组织中MIP-2、IL-10和IL-18蛋白的表达水平。结果 Res组在造模后12 h,肺组织病理变化与Sep组相比有所减轻,48 h Res作用达到最强,各种病理改变明显减轻,部分肺组织开始接近正常形态;肺组织W/D比值与Sep组相比均明显降低(P<0.05);Res组在12、24和48 h MIP-2水平均明显低于同时间点Sep组(P<0.05),在24和48 h IL-10水平明显低于同时间点Sep组(P<0.05),12、24和48 h IL-18水平明显低于同时间点Sep组(P<0.05)。Western blot结果显示,造模后24 h,Res组MIP-2、IL-10和IL-18蛋白表达水平明显低于Sep组(P<0.05)。结论白藜芦醇能有效减轻脓毒症所致ALI,作用与抑制MIP-2、IL-10和IL-18的过度表达,实现内稳态有关。

Objective To investigate the protective effect of resveratrol on rats with acute lung injury（ALI）induced by sepsis and its influence on the expressions of macrophage inflammatory protein-2（MIP-2）,interleukin-10（IL-10）and interleukin-18（IL18）in the injured lung tissue.Methods SD rats were randomly divided into contro（l Con）,sham operation（Sham）,sepsis（Sep） and resveratrol（Res）groups.Sepsis-induced ALI model was established by cecal ligation and puncture（CLP）,and then,24 h later,the rats in Res group were injected i.v.with resveratrol at a dosage of 0.3 ml / 100 g,while those in Con,Sham and Sep groups with physiological saline each at an equal volume.The lung tissues of rats in various groups were collected 0,6,12,24 and 48 h after successful modeling,and observed for morphological change by HE staining,based on which the wet / dry weight（W / D） ratio of lung was calculated.The MIP-2,IL-10 and IL-18 contents in plasma of rats in various groups were determined by ELISA,while their expression levels in lung tissue by Western blot.Results The pathological change of lung tissues of rats in Res group 12 h after modeling was relieved as compared with those in Sep group,while the morphology of partial lung tissue was nearly normal 48 h after modeling.The W / D ratios of rats in Res groups at various time points were significantly lower than those in Sep group（P 〈 0.05）.The MIP-2 levels of rats in Res group 12,24 and 48 h after modeling were significantly lower than those in Sep group（P 〈 0.05）.The IL-10 levels of rats in Res group 24 and 48 h as well as the IL-18 levels 12,24 and 48 h after modeling were significantly lower than those in Sep group（P 〈 0.05）.Western blot showed that the expression levels of MIP-2,IL-10 and IL-18 in Res group 24 h after modeling were significantly lower than those in Sep group（P 〈 0.05）.Conclusion Resveratrol effectively relieved the ALI induced by sepsis,which might be associated with the inhibition of overexpressions of MIP-2,L-10 and IL-18.