目的 探究川黃連Coptis chinensis Franch.調(diào)控絲裂原活化蛋白激酶(MAPK)/胞外信號調(diào)節(jié)激酶(ERK)通路對口腔潰瘍大鼠微循環(huán)及Th1/Th2細胞水平的作用。方法 將大鼠隨機分為對照組、模型組、西瓜霜(200 mg·kg^-1組和川黃連20、40、80 mg·kg^-1組,每組10只。除對照組外,采用40%冰醋酸灼燒法制備口腔潰瘍模型,各給藥組涂抹給藥,每2天給藥1次,連續(xù)給藥7 d。比較各組大鼠口腔潰瘍面積;腹主動脈取血檢測微循環(huán)指標[微量毛細管法測定紅細胞壓積(HCT),試劑盒法檢測血清纖維蛋白原(FIB)水平,椎板式黏度計測定血漿黏度];ELISA法檢測血清中炎癥因子白細胞介素-6(IL-6)、IL-8和腫瘤壞死因子-α(TNF-α)水平及血清中Th1/Th2細胞相關(guān)因子γ-干擾素(IFN-γ)、IL-10水平;HE染色觀察潰瘍黏膜組織病理學變化;Western blotting檢測黏膜組織中ERK1/2、p-ERK1/2、p38 MAPK、p-p38 MAPK蛋白表達。結(jié)果 與模型組比較,川黃連20、40、80 mg·kg^-1組口腔潰瘍面積均顯著減少(P＜0.05),黏膜上皮細胞溶解、炎癥反應、組織壞死等病理學改變明顯減輕;HCT、FIB、血漿黏度均顯著降低(P＜0.05);血清中炎癥因子IL-6、IL-8、TNF-α水平均顯著降低(P＜0.05);血清中IFN-γ和IFN-γ/IL-10水平顯著降低,IL-10水平明顯升高(P＜0.05);ERK1/2、p-ERK1/2、p38MAPK、p-p38 MAPK蛋白表達均顯著降低(P＜0.05),且川黃連80 mg·kg^-1作用最明顯。結(jié)論 川黃連可改善口腔潰瘍大鼠微循環(huán),維持Th1/Th2細胞在體內(nèi)平衡狀態(tài),其作用機制可能與抑制MAPK/ERK通路相關(guān)。

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

湖北省中央引導地方科技發(fā)展專項(編號2020ZYYD030)