外源性一氧化氮调控MEK/ERK信号通路促进胃溃疡大鼠黏膜修复的实验观察  

Observation of exogenous nitric oxide regulates MEK/ERK signal pathway and promotes mucosal repair in gastric ulcer rats

作　　者：顾俊骏 李兴华[1] GU Jun-jun;LI Xing-hua(Department of Gastroenterology,The Eighth People＇s Hospital of Shanghai,Shanghai 200235,China)

机构地区：[1]上海市第八人民医院消化内科,上海200235

出　　处：《临床和实验医学杂志》2018年第22期2378-2382,共5页Journal of Clinical and Experimental Medicine

摘　　要：目的观察外源性一氧化氮(NO)通过调控丝裂原细胞外信号调节激酶(MEK)/细胞外信号调节激酶(ERK)信号通路促进胃溃疡(GU)大鼠黏膜修复作用。方法取40只大鼠以冰醋酸法建立GU大鼠模型,并将其随机分为模型组、低、中、高剂量组,另取10只大鼠注射生理盐水,设为对照组。术后低、中、高剂量组腹腔注射NO外源性供体硝普钠(SNP) 2 mg/kg、4 mg/kg、6 mg/kg,对照组和模型组腹腔注射等体积生理盐水,2次/d,连续3 d。第4天处死大鼠,进行组织病理学观察,对比溃疡面积、溃疡抑制率,并对比表皮生长因子受体(EGFR)、大鼠肉瘤相关因子(Raf)、MEK、ERK mRNA相对表达量、磷酸化EGFR(pEGFR)/EGFR、磷酸化Raf(pRaf)/Raf、磷酸化MEK(pMEK)/MEK、磷酸化ERK(pERK)/ERK及紧密连接蛋白1(ZO-1) mRNA和蛋白相对表达量。结果组织病理学观察发现,3剂量组炎性细胞浸润程度较模型组减轻,且中剂量组减轻程度最为明显;溃疡面积组间比较,中剂量组最低、低、高剂量组其次、模型组最高,除低、高剂量组比较差异无显著性(P> 0. 05)外,每两组间比较差异有显著性(P <0. 05),中剂量组溃疡抑制率显著高于低、高剂量组(P <0. 05),低、高剂量组溃疡抑制率比较无显著性(P> 0. 05);溃疡组织EGFR、Raf、MEK、ERK mRNA相对表达量、pEGFR/EGFR、pRaf/Raf、p MEK/MEK、pERK/ERK及ZO-1 mRNA和蛋白相对表达量组间比较,对照组最高、中剂量组其次、低、高剂量组稍高、模型组最低,除低、高剂量组比较无显著性(P> 0. 05)外,每两组间比较差异均有显著性(P <0. 05)。结论外源性NO供体SNP可促进GU大鼠黏膜修复,其中4 mg/kg的SNP促进效果最佳,推测与上调EGFR、Raf、MEK、ERK mRNA,ZO-1 mRNA和蛋白相对表达量,pEGFR/EGFR、pRaf/Raf、pMEK/MEK、pERK/ERK,激活MEK/ERK信号通路有关。Objective To observe the effect of exogenous nitric oxide （NO） on mucosal repair in gastric ulcer （GU） rats by regulating mitogen - derived extracellular signal - regulated kinase （MEK）/extracellular signal - regulated kinase （ERK） signaling pathway. Methods 40 GU rats were established by glacial acetic acid method and randomly divided into model group, low, medium and high dose group. Another 10 saline injections were used as control group. Rats in the low, middle and high dose groups were given intraperitoneal injections of NO exogenous donor sodium nitroprusside （SNP） 2, 4, 6 mg/kg, and the control and model groups were given intraperitoneal injection of an equal volume of normal saline twice a day, continuous injection for 3 days. The rats were sacrificed on the 4th day after operation for histopathological observation, and the ulcer areas and ulcer inhibition rates were compared. The relative mRNA expressions of epidermal growth factor receptor （EGFR） , rat sarcoma - associated factor （Raf） MEK, ERK, phosphorylated EGFR （ pEGFR）/EGFR, phosphorylated Raf （ pRaf）/Raf, phosphorylated MEK （pMEK）/MEK, phosphorylated ERK （pERK） , and the relative lnRNA and protein expressions of ZO - 1 were compared. Results Histopathological observations revealed that the inflammatory cells infiltration were reduced of the 3 dose groups, and the degree of reduction in the middle dose group was the most obvious. The ulcer areas were compared between each 2 groups, and the ulcer area of the middle dose group were the lowest, the low and high dose groups slightly higher, the model group highest. Tbere were significant differences between each 2 groups （ P 〈 0.05） , without differences between the low and high dose groups （ P 〉 0.05 ）. The ulcer inhibition rate of the middle dose group was significantly higher than that of the low and high dose groups （ P 〈 0.05 ）. There were no significant differences in the ulcer inhibition rates between low and high dose groups （ P �

关 键 词：大鼠 胃溃疡 外源性一氧化氮 丝裂原细胞外信号调节激酶 细胞外信号调节激酶 黏膜修复 

分 类 号：R573.1[医药卫生—消化系统]