川黄连调控MAPK/ERK通路对口腔溃疡大鼠微循环及Th1/Th2细胞因子的作用  

Study on mechanism of Coptis chinensis regulating MAPK/ERK pathway in microcirculation and Th1/Th2 cytokines in rats with oral ulcers

作　　者：刘苗苗 崔月曦 郑勇 刘艳菊 LIU Miaomiao;CUI Yuexi;ZHENG Yong;LIU Yanju(Department of Pharmacy,Hubei Integrated Traditional Chinese and Western Medicine Hospital,Wuhan 430010,China;School of Pharmacy,Hubei University of Traditional Chinese Medicine,Wuhan 430072,China)

机构地区：[1]湖北省中西医结合医院药学部,湖北武汉430010 [2]湖北中医药大学药学院,湖北武汉430072

出　　处：《药物评价研究》2024年第2期323-330,共8页Drug Evaluation Research

基　　金：湖北省中央引导地方科技发展专项(编号2020ZYYD030)。

摘　　要：目的探究川黄连Coptis chinensis Franch.调控丝裂原活化蛋白激酶(MAPK)/胞外信号调节激酶(ERK)通路对口腔溃疡大鼠微循环及Th1/Th2细胞水平的作用。方法将大鼠随机分为对照组、模型组、西瓜霜(200 mg·kg^(-1))组和川黄连20、40、80 mg·kg^(-1)组,每组10只。除对照组外,采用40%冰醋酸灼烧法制备口腔溃疡模型,各给药组涂抹给药,每2天给药1次,连续给药7 d。比较各组大鼠口腔溃疡面积;腹主动脉取血检测微循环指标[微量毛细管法测定红细胞压积(HCT),试剂盒法检测血清纤维蛋白原(FIB)水平,椎板式黏度计测定血浆黏度];ELISA法检测血清中炎症因子白细胞介素-6(IL-6)、IL-8和肿瘤坏死因子-α(TNF-α)水平及血清中Th1/Th2细胞相关因子γ-干扰素(IFN-γ)、IL-10水平;HE染色观察溃疡黏膜组织病理学变化;Western blotting检测黏膜组织中ERK1/2、p-ERK1/2、p38 MAPK、p-p38 MAPK蛋白表达。结果与模型组比较,川黄连20、40、80 mg·kg^(-1)组口腔溃疡面积均显著减少(P<0.05),黏膜上皮细胞溶解、炎症反应、组织坏死等病理学改变明显减轻;HCT、FIB、血浆黏度均显著降低(P<0.05);血清中炎症因子IL-6、IL-8、TNF-α水平均显著降低(P<0.05);血清中IFN-γ和IFN-γ/IL-10水平显著降低,IL-10水平明显升高(P<0.05);ERK1/2、p-ERK1/2、p38MAPK、p-p38 MAPK蛋白表达均显著降低(P<0.05),且川黄连80 mg·kg^(-1)作用最明显。结论川黄连可改善口腔溃疡大鼠微循环,维持Th1/Th2细胞在体内平衡状态,其作用机制可能与抑制MAPK/ERK通路相关。Objective To investigate the mechanism of Coptis chinensis Franch.mediated mitogen activated protein kinase(MAPK)/extracellular signal regulated kinase(ERK) on microcirculation and Th1/Th2 cell levels in rats with oral ulcers.Methods The rats were randomly divided into control group,model group,Coptis chinensis 20,40,80 mg · kg^(-1) group,and watermelon cream(200 mg·kg^(-1)) group,with 10 rats in each group.Except for the control group,oral ulcer models were prepared using the burning method with 40% acetic acid.Each treatment group was coated and administered once every 2 days for 7 consecutive days.Blood samples were taken from the abdominal aorta to detect microcirculation indicators.Hematocrit(HCT) was measured using a microcapillary method,serum fibrinogen(FIB) levels were measured using a reagent kit method,and plasma viscosity was measured using a vertebral plate viscometer.Serum levels of inflammatory factors interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α) and serum levels of Th1,Th2 cell-related factors IFN-γ and IL-10 were detected by ELISA.The histopathological changes of ulcer mucosa were observed by HE staining.The expression of ERK1/2,p-ERK1/2,p38 MAPK and pp38 MAPK in mucosal tissues was detected by Western blotting.Results Compared with the model group,the oral ulcer area of Coptis chinensis 20,40,80 mg·kg^(-1) group was significantly reduced(P < 0.05),and pathological changes such as mucosal epithelial cell lysis,inflammatory response,and tissue necrosis were significantly reduced,HCT,FIB,and plasma viscosity were significantly reduced(P < 0.05),the levels of inflammatory factors IL-6,IL-8,and TNF-α in serum were significantly reduced(P < 0.05).The level of IFN-γ and IFN-γ/IL-10 in serum significantly decreased,while the level of IL-10 significantly increased(P < 0.05).The expression of ERK1/2,p-ERK1/2,p38 MAPK,and p-p38 MAPK proteins was significantly reduced(P < 0.05),and the effect of Coptis chinensis 80 mg·kg^(-1) was the most significant.Conclusion Coptis chi

关 键 词：川黄连 MAPK/ERK通路 口腔溃疡 微循环 TH1/TH2细胞因子 炎症 

分 类 号：R285.5[医药卫生—中药学]