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 chinensis can improve microcirculation in rats with oral ulcers, maintain a balanced state of Th1/Th2 cells in the body, which may be related to the inhibition of the MAPK/ERK pathway.

R285.5

湖北省中央引导地方科技发展专项(编号2020ZYYD030)