AngⅡ激活P38MAPK信号通路在大鼠NSAID相关小肠损伤中的机制研究  

Study on the mechanism of AngⅡactivated P38MAPK signaling pathway in small intestine injury induced by NSAID in rats

作　　者：钱瑾[1] 孟立娜[2] QIAN Jin;MENG Lina(Department of Gastroenterology,Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015,China;Department of Gastroenterology,First Affiliated Hospital,Zhejiang Chinese Medical University,Key Laboratory of Pathophysiology of Digestive Tract Diseases in Zhejiang,Institute of Digestive Diseases,Zhejiang Chinese Medical University,Hangzhou 310006,China)

机构地区：[1]杭州师范大学附属医院消化内科,浙江杭州310015 [2]浙江中医药大学附属第一医院消化内科,浙江省消化道疾病病理生理重点实验室,浙江中医药大学消化病研究所,浙江杭州310006

出　　处：《中国现代医生》2022年第19期1-5,共5页China Modern Doctor

基　　金：国家自然科学基金资助项目(81373877);浙江省自然科学基金资助项目(Y2100969)。

摘　　要：目的探讨血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)激活P38丝裂原活化蛋白激酶(P38 mitogen–activated protein kinase,P38MAPK)信号通路在大鼠非甾体抗炎药(nonsteroidal anti–inflammatory drug,NSAID)相关小肠损伤中的作用机制。方法将16只SD大鼠随机分为对照组和模型组,每组各8只,对照组大鼠给予生理盐水10ml/(kg·d),模型组大鼠给予双氯芬酸7.8mg/(kg·d),两组大鼠均连续灌胃5d建立大鼠NSAID小肠损伤模型。观察两组大鼠小肠黏膜的大体形态及病理组织学损伤,并进行损伤指数评分。蛋白质印迹法检测小肠组织中p–P38MAPK蛋白表达,免疫组织化学法检测小肠组织中AngⅡ、p–P38MAPK及细胞间黏附分子–1(intercelluar adhesion molecule–1,ICAM–1)的表达,并进行相关性分析。结果对照组大鼠小肠黏膜未见明显的肉眼及病理组织学损伤,模型组大鼠小肠黏膜均出现不同程度的充血、水肿、糜烂及溃疡形成,苏木精–伊红染色见小肠组织上皮结构消失、绒毛坏死脱落、毛细血管充血及淋巴管扩张伴大量炎症细胞浸润,大体形态损伤指数及病理损伤指数均显著高于对照组(均P<0.05)。蛋白质印迹法结果显示,模型组大鼠p–P38MAPK表达显著高于对照组(P<0.01)。免疫组织化学结果显示,模型组大鼠AngⅡ、p–P38MAPK和ICAM–1表达均显著高于对照组(均P<0.01)。AngⅡ、p–P38MAPK及ICAM–1的表达均与小肠黏膜组织学损伤程度呈正相关(均P<0.01),AngⅡ与p–P38MAPK、p–P38MAPK与ICAM–1的表达均呈正相关(均P<0.01)。结论应用双氯芬酸短期内给大鼠灌胃即可致大鼠小肠损伤,其发病机制可能是AngⅡ激活P38MAPK信号通路后,上调ICAM–1表达,从而介导NSAID小肠损伤。Objective To explore mechanism of angiotensin Ⅱ(AngⅡ) activated P38 mitogen-activated protein kinase(P38 MAPK) signaling pathway in small intestine injury induced by nonsteroidal anti-inflammatory drug(NSAID) in rats. Methods Sixteen Sprague-Dawley rats were randomly divided into control group(n=8) and model group(n=8). Rats in control group were given normal saline 10 ml/(kg·d), and rats in model group were given diclofenac 7.8 mg/(kg·d). Rats in both groups were intragastric for 5 days to establish rat model of small intestinal injury with NSAID. The gross morphology and histological lesions of small intestinal mucosa of rats in each group were observed, and the injury index was scored. The expression of p–P38 MAPK protein in small intestine was measured by Western blotting, the expression of AngⅡ, p–P38 MAPK and intercelluar adhesion molecule–1(ICAM–1) in small intestine were detected by immunohistochemistry, then analyzed their correlation. Results There were no obvious macroscopical and histopathological lesions in the small intestinal mucosa of control group. The small intestinal mucosa of model group showed varying degrees of hyperemia 、edema 、erosion and ulceration,hematoxylin and eosin staining showed disappearance of epithelial structure, necrosis and shedding of villi, hyperemia of capillaries and lymphatic dilatation with a large number of inflammatory cells. The gross morphological injury index and pathological injury index were significantly higher than that of the control group(all P<0.05). Western blotting results showed that the expression of p–P38 MAPK in model group was significantly higher than that in control group(P<0.01). Immunohistochemical results showed that AngⅡ, p–P38 MAPK and ICAM–1 expression in model group were significantly higher than those in control group(all P<0.01). The expressions of AngⅡ,p–P38 MAPK and ICAM–1 were positively correlated with the degree of histological injury of small intestinal mucosa(all P<0.01), and the expressions of Ang�

关 键 词：非甾体抗炎药 小肠 血管紧张素Ⅱ P38丝裂原活化蛋白激酶 细胞间黏附分子-1 

分 类 号：R574[医药卫生—消化系统]