Ang(1-7)通过调节Treg/Th17平衡参与保护NSAIDs相关小肠损伤  

Protective Effect of Ang(1-7)on Small Intestinal Injury in NSAIDs-induced Enteropathy by Regulating Treg/Th17 Balance

作　　者：潘宜久 王连魁 熊华 PAN Yijiu;WANG Liankui;XIONG Hua(Department of Gastroenterology,Ningbo Hangzhou Bay Hospital,Ningbo,Zhejiang Province 315336;Division of Gastroenterology and Hepatology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai Institute of Digestive Disease,Shanghai)

机构地区：[1]宁波市杭州湾医院消化内科,315336 [2]上海交通大学医学院附属仁济医院消化内科,上海市消化疾病研究所

出　　处：《胃肠病学》2021年第7期395-401,共7页Chinese Journal of Gastroenterology

摘　　要：背景:非甾体抗炎药(NSAIDs)广泛应用于临床。随着内镜技术的进步,NSAIDs相关小肠损伤越来越多见,但目前尚无明确有效的防治措施。目的:探讨调节性T细胞(Treg细胞)与Th17细胞失衡在NSAIDs相关小肠损伤中的作用以及血管紧张素1-7[Ang(1-7)]的保护效应。方法:30只雄性Sprague-Dawley大鼠随机分为对照组、模型组和Ang(1-7)治疗组,后两组使用双氯芬酸钠诱导小肠损伤模型。5 d后处死大鼠,取小肠黏膜观察大体和组织学损伤情况;以ELISA法和(或)免疫组化法检测Ang(1-7)以及促炎和抗炎细胞因子水平;流式细胞术分析Treg、Th17细胞占CD4+T细胞的比例。结果:模型组大鼠小肠黏膜广泛充血、水肿,散在多发糜烂、小溃疡。Ang(1-7)治疗组小肠损伤明显减轻,黏膜轻度充血、水肿,散在少量小糜烂灶。治疗组小肠组织Ang(1-7)、抗炎细胞因子水平、Treg细胞数量和Treg/Th17比值较模型组显著升高,抗炎细胞因子水平和Th17细胞数量较模型组显著降低(P均<0.05)。Pearson相关系数分析显示,小肠黏膜Ang(1-7)含量与Treg/Th17比值呈显著正相关(r=0.847,P<0.05)。结论:Treg/Th17失衡可能是NSAIDs相关小肠损伤的重要发病机制,而Ang(1-7)可能通过调节Treg/Th17平衡参与保护NSAIDs相关小肠损伤。Background:Nonsteroidal antiinflammatory drugs(NSAIDs)are widely used in clinical practice.As the progress of endoscopic techniques,NSAIDs-induced small intestinal injury is more frequently to be detected,but there is still lack of effective preventive and therapeutic measures.Aims:To explore the role of regulatory T cells(Treg cells)/Th17 cells imbalance in NSAIDs-induced small intestinal injury and the protective effect of angiotensin 1-7[Ang(1-7)].Methods:Thirty male Sprague-Dawley rats were randomly divided into control group,model group,and Ang(1-7)treatment group;in the latter two groups,diclofenac sodium was used to induce small intestinal injury.On day 5,the rats were sacrificed to obtain small intestinal mucosa.The macro-and microscopic changes of the intestinal mucosa were evaluated;the levels of Ang(1-7),and pro-and antiinflammatory cytokines were detected by ELISA and/or immunohistochemistry;flow cytometry was used to determine the proportions of Treg and Th17 cells in CD4+T cells.Results:Diffused hyperemia and edema,and scattered ulcerative erosions were observed in small intestinal mucosa in model group.While in Ang(1-7)treatment group,the abovementioned damages were ameliorated,mild hyperemia and edema,and fewer erosions were observed without ulcer formation.Furthermore,the tissue levels of Ang(1-7),antiinflammatory cytokines,proportion of Treg cells,and Treg/Th17 ratio were increased,whereas the tissue levels of proinflammatory cytokines and proportion of Th17 cells were decreased in Ang(1-7)treatment group as compared with those in model group(all P<0.05).Pearson correlation coefficient analysis revealed a positive correlation between Ang(1-7)level and the ratio of Treg/Th17 cells(r=0.847,P<0.05).Conclusions:Treg/Th17 imbalance might be involved in the pathogenesis of small intestinal injury in NSAIDs-induced enteropathy.Ang(1-7)might exert a protective effect on NSAIDs-induced small intestinal injury by regulating Treg/Th17 balance.

关 键 词：小肠损伤 消炎药 非甾类 T淋巴细胞 调节性 Th17细胞 血管紧张素1-7 

分 类 号：R73[医药卫生—肿瘤]