吉法酯通过调控P38MAPK信号通路对NSAIDs小肠损伤防治作用的实验研究  

Experimental study on the preventive and therapeutic effect of gifaxone on small intestine injury of NSAIDs by regulating P38MAPK signaling pathway

作　　者：钱瑾[1] 孟立娜[2] QIAN Jin;MENG Lina(Department of Gastroenterology,Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015,Zhejiang,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 University of Chinese Medicine,Hangzhou 310006,Zhejiang,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》2023年第3期17-20,41,共5页China Modern Doctor

基　　金：浙江省自然科学基金项目(Y2100969)。

摘　　要：目的观察胃黏膜保护药吉法酯对非甾体类抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)相关小肠损伤的防治作用,并探讨其可能机制。方法24只SD大鼠随机分为对照组、双氯芬酸模型组和吉法酯干预组,每组8只;对照组和模型组分别给予生理盐水10ml/(kg·d)和双氯芬酸7.8mg/(kg·d)灌胃,吉法酯干预组在造模前1d给予吉法酯31.25mg/(kg·d)灌胃,造模当日起,先予吉法酯31.25mg/(kg·d)灌胃,1h后再予双氯芬酸7.8mg/(kg·d)灌胃,连续造模5d后处死所有大鼠,比较各组大鼠小肠黏膜大体及病理损伤情况并评分。免疫印迹法检测小肠组织中磷酸化P38丝裂原活化蛋白激酶(p-P38 mitogen-activated protein kinase,p-P38MAPK)蛋白的表达,免疫组化法检测小肠组织中细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的表达。结果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,镜下可见小肠上皮结构破坏,绒毛坏死脱落,毛细血管充血,淋巴管扩张及大量炎症细胞浸润,大体和病理损伤评分均较对照组显著升高(P<0.01),而吉法酯干预组小肠黏膜的损伤程度较模型组明显减轻(P<0.05)。免疫印迹法结果显示,模型组小肠组织中p-P38MAPK蛋白的表达显著高于对照组(P<0.01),吉法酯干预组较模型组显著降低(P<0.01)。免疫组化结果显示,ICAM-1在模型组中的表达显著高于对照组(P<0.01),而在吉法酯干预组中的表达较模型组显著下降(P<0.05)。结论吉法酯对NSAIDs小肠黏膜损伤具有一定的防治作用,可有效减轻小肠黏膜损伤,其机制可能与抑制P38MAPK信号通路、下调ICAM-1的表达有关。Objective To observe the preventive and therapeutic effect of gefarnate on non steroidal anti-inflammatory drugs(NSAIDs) induced small intestinal injury, and evaluate its possible mechanism. Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups, namely normal control group(n=8), diclofenac model group(n=8) and gefarnate therapy group(n=8). The rats of normal control group were given normal saline 10ml/(kg·d) by intragastric administration for five days,rats in model control group were received 7.8mg/(kg·d) diclofenac for five days, rats in gefarnate therapy group were first given 31.25mg/(kg·d) gefarnate one day before modeling, then on the next day, given the same dose for once, an hour before 7.8mg/(kg·d) diclofenac for five days. The specimens of small intestinal mucosa were taken out 24hours after the last drug intragastric administration to observe the morphological and histological lesions. Used western blot to measure the activity of phosphorylated p-P38MAPK and immunohistochemistry to stain the specimens to observe phosphorylated p38MAPK and intercellular adhesion molecule-1(ICAM-1) for microscopic analysis. Results In the model group, the small intestinal mucosa of rats showed different degrees of hyperemia, edema, erosion and ulceration. Under microscope, the different degrees of intestinal epithelial structure destruction and intestinal villi necrosis, capillary congestion and the expansion of lymphatic vessels,accompanied with a large number of inflammatory cell infiltration were appeared. Compared with the control group, the gross and pathological injury scores were significantly increased(P<0.01), while the injury degree of small intestinal mucosa in the gefaramate intervention group was significantly reduced compared with the model group(P<0.01). Western blot results showed that the expression of p-P38MAPK protein in the small intestine of the model group was significantly higher than that of the control group(P<0.01), and the gefaramate intervention group was signific

关 键 词：非甾体类抗炎药 小肠 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]