槲皮素抑制LPS诱导的大鼠急性肺损伤和巨噬细胞的促炎表型  

Quercetin attenuates LPS-induced acute lung injury and the pro-inflammatory phenotype of macrophages in rats

作　　者：李桂荣 沈忱悠 卫栋[1] 陈静瑜[1] LI Guirong;SHEN Chenyou;WEI Dong;CHEN Jingyu(Laboratory of Organ Transplantation Research Institute,Wuxi People′s Hospital,Wuxi 214023,China)

机构地区：[1]无锡市人民医院器官移植研究院实验室,江苏无锡214023

出　　处：《宁夏医学杂志》2023年第5期389-392,I0001,共5页Ningxia Medical Journal

基　　金：江苏省自然科学基金青年项目(BK20190150)。

摘　　要：目的探究槲皮素对脂多糖(LPS)诱导的急性肺损伤大鼠的保护作用,探讨其作用机制。方法30只SD大鼠随机分成对照组、脂多糖组,脂多糖+槲皮素组。大鼠气管滴注给予LPS(5 mg/kg)溶液24 h,诱导急性肺损伤,对照组气管滴注等体积PBS溶液,治疗组给予LPS和腹腔注射槲皮素(50 mg/kg)溶液。HE染色观察肺组织的病理变化、肺组织湿干比检测水肿程度qRT-PCR方法检测肺组织炎症因子TNF-α和IL-1β的表达。免疫组织化学法检测肺组织中巨噬细胞标志蛋白CD68的表达与分布。Western blot法检测肺组织中巨噬细胞表型促炎标志蛋白IRF5和抑炎标志蛋白Arg1的表达及Notch1蛋白表达变化。结果LPS刺激大鼠肺组织后呈现炎症损伤,肺组织湿干比增加,炎症因子TNF-α和IL-1β的mRNA水平显著增加(P<0.05);给予槲皮素后,肺组织湿干比降低,炎症因子表达下调,抑制了肺组织炎症损伤。LPS刺激肺组织后,CD68蛋白和促炎标志蛋白IRF5表达上调(P<0.05),肺组织巨噬细胞发生浸润和呈现促炎表型;而槲皮素抑制了LPS诱导的CD68和IRF5表达(P<0.05)。结论槲皮素抑制了LPS诱导的大鼠急性肺损伤的炎症反应,巨噬细胞浸润和巨噬细胞的促炎表型,槲皮素对LPS诱导的急性肺损伤大鼠有保护作用。Objective To observe the protective effect of quercetin in acute lung injury induced by lipopolysaccharide(LPS)and its mechanism.Methods Thirty SD rats were randomly divided into control group,LPS group and quercetin+LPS group.The model of acute lung injury in rats was established by tracheal instillation LPS(5mg/kg)and the control group was instilled with equal volume of PBS.The treatment group was given LPS solution and intraperitoneal injection of quercetin(50 mg/kg)solution.The pathological changes of lung tissue used by HE staining,the degree of edema used by wet/dry ratio and the expression of inflammatory factor used by qRT-PCR were investigated.The expression and distribution of macrophage marker protein CD68 in lung tissue was detected by immunohistochemistry(IHC)method.The expression of pro-inflammatory macrophage phenotypic marker protein IRF5,anti-inflammatory macrophage phenotypic marker protein Arg1 and Notch1 protein were detected by Western blot.Results Lung tissue of rat stimulated by LPS showed inflammation.Lung tissue wet/dry ratio was increased,and the mRNA levels of inflammatory factors TNF-αand IL-1β were significantly increased(P<0.05).Whereas the wet/dry ratio,the expression of pro-inflammatory factors and inflammatory injury of lung tissues were inhibited after quercetin treatment.After LPS stimulation,the expressions of CD68 protein and pro-inflammatory marker protein IRF5 were up-regulated(P<0.05),and lung macrophages were infiltrated and showed pro-inflammatory phenotype.Quercetin inhibited the expression of CD68 and IRF5 induced by LPS(P<0.05).Conclusion Quercetin could inhibit the inflammatory response,macrophage infiltration,proinflammatory phenotype of macrophages in rats with LPS-induced acute lung injury.Quercetin has a protective effect on rats with LPS-induced acute lung injury.

关 键 词：急性肺损伤 槲皮素 巨噬细胞 炎症反应 

分 类 号：R965[医药卫生—药理学]