Ghrelin对脓毒症肺损伤大鼠肺泡巨噬细胞及肺组织iNOS表达的影响  

Effect of ghrelin on iNOS expression in alveolar macrophages and lung tissues in rats with sepsis-associated lung injury

作　　者：何婉媚[1] 曾勉[1] 易慧[1] 蒋玉洁[1] 常敏婵[1] 

机构地区：[1]中山大学附属第一医院MICU,广东广州510080

出　　处：《中国病理生理杂志》2013年第5期895-899,共5页Chinese Journal of Pathophysiology

基　　金：广东省科技计划(No.2008B030301057)

摘　　要：目的:观察ghrelin对脓毒症肺损伤大鼠肺泡巨噬细胞及肺组织诱导型一氧化氮合酶(inducible ni-tric oxide synthase,iNOS)表达的影响。方法:SD雄性大鼠分为假手术组、脓毒症组及ghrelin治疗组,前2组各设术后6 h、12 h和20 h亚组。通过盲肠结扎穿孔术(cecal ligation and puncture,CLP)建立脓毒症模型,ghrelin治疗组于术后3 h及15 h腹腔注射ghrelin,术后20 h取材。各组按术后既定时间行支气管肺泡灌洗收集肺泡巨噬细胞,RT-PCR检测肺泡巨噬细胞中iNOS mRNA的表达水平。另一部分大鼠则在术后20 h采集右肺,行肺病理学检查及Western blotting检测肺组织iNOS蛋白表达。结果:脓毒症组在CLP术后6 h、12 h和20 h肺泡巨噬细胞iNOSmRNA的表达水平分别为1.33±0.05、1.44±0.08和1.57±0.11,均高于假手术组(P<0.05),并不随时间延长而升高;但在术后20 h却低于ghrelin治疗组(2.27±0.37;P<0.05)。Ghrelin治疗组CLP术后20 h肺组织iNOS蛋白表达水平(0.87±0.03)低于脓毒症组(P<0.05)。Ghrelin治疗组肺组织病理学评分(5.83±0.477)较脓毒症组(7.83±0.75)低,2组均高于假手术组(P<0.05)。结论:CLP术后6～20 h,大鼠肺泡巨噬细胞iNOS mRNA的表达水平升高,但无时间依赖性。Ghrelin对脓毒症大鼠肺泡巨噬细胞iNOS mRNA表达起上调作用,而对肺组织iNOS蛋白表达起抑制作用,减轻肺损伤程度。AIM： To investigate the effect of ghrelin on inducible nitric oxide synthase （iNOS） expression in alveolar macrophages and lung tissues in sepsis-induced acute lung injury （ALI） rats. METHODS： The septic rat model was established by cecal ligation and puncture （CLP）. Male SD rats were divided into sham group, CLP group and CLP ＋ ghrelin group. The rats in the former 2 groups were further divided into 3 subgroups, which were 6 h, 12 h and 20 h post- operation groups. Ghrelin was administered by intraperitoneal injection at 3 h and 15 h after operation in ghrelin group. The samples were harvested 20 h after operation. The mRNA expression of iNOS in alveolar macrophages collected from bron- choalveolar lavage was detected by RT-PCR. The protein levels of lung iNOS were measured by Western blotting. The lung pathological examination was performed 20 h after operation. RESULTS： In CLP group, the mRNA expression levels of iNOS in the alveolar macrophages were 1.33 ± 0.05, 1.44± 0.08, 1.57 ± 0.11 at 6 h, 12 h and 20 h after CLP, respec- tively, which were higher than that in sham group, but did not show time correlation. However, it was lower in CLP group than that in CLP ＋ ghrelin group at 20 h after CLP （2.27 ±0.37, P 〈0.05）. At 20 h after CLP, the protein level of lung iNOS was decreased in CLP ＋ ghrelin group （0.87 ± 0.03） as compared with CLP group （ 1.08 ±0.05）. Compared with sham group, the histopathological score was increased in both CLP group and CLP ＋ ghrelin group, but it was lower in CLP ＋ ghrelin group （5.83 ± 0. 477 ） than that in CLP group （7.83 ± 0.75 ）. CONCLUSION： Ghrelin treatment improves the degree of ALI. During 6 h to 20 h after CLP, the mRNA expression of iNOS in alveolar macrophages was elevated, but thedifference was not seen as the time went on. Ghrelin up-regulates the mRNA expression of iNOS in alveolar macrophages and inhibits iNOS expression in lungs of septic rats.

关 键 词：GHRELIN 脓毒症 肺损伤 一氧化氮合酶 肺泡巨噬细胞 

分 类 号：R515.3[医药卫生—内科学]