首页|基于ERK/p38 MAPK信号通路探讨雷公藤多苷对溃疡性结肠炎大鼠的保护作用

基于ERK/p38 MAPK信号通路探讨雷公藤多苷对溃疡性结肠炎大鼠的保护作用

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探讨雷公藤多苷对溃疡性结肠炎大鼠的影响,并研究细胞外信号调节激酶/p38 丝裂原活化蛋白激酶(extracellular signal-regulated kinase/p38 mitogen-activated protein kinase,ERK/p38 MAPK)信号通路的调控作用.选取 70 只雄性Wistar大鼠作为研究对象,将其随机分为对照组,模型组,雷公藤多苷低、中、高剂量组,阳性对照组,通路抑制剂组.观察各组大鼠疾病活动指数(disease activity index,DAI)评分、大体形态损伤评分、镜下结肠损伤评分;采用HE染色检测各组大鼠结肠组织病理变化;采用TUNEL法检测各组大鼠肠黏膜细胞凋亡率;采用ELISA法检测各组大鼠血清白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)及肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平;采用蛋白免疫印迹(Western blot)和PCR法检测各组大鼠结肠组织中ERK/p38 MAPK通路相关蛋白和mRNA表达.结果显示,雷公藤多苷可有效改善组织病理学情况;与对照组相比,模型组小鼠DAI评分,形态损伤评分,结肠损伤评分,结肠黏膜细胞凋亡率,血清中IL-1β、IL-6、TNF-α水平,结肠组织中p-ERK/ERK、p-p38 MAPK/p38 MAPK水平,结肠组织中ERK、p38 MAPK mRNA水平显著升高(P<0.05);与模型组相比,雷公藤多苷高剂量组、阳性对照组和通路抑制剂组大鼠DAI评分降低,通路抑制剂组最低(P<0.05);与模型组相比,其余各组形态损伤评分、结肠损伤评分降低,通路抑制剂组最低(P<0.05);与模型组相比,雷公藤多苷高剂量组、阳性对照组、通路抑制剂组大鼠肠黏膜细胞凋亡率降低,血清中IL-1β、IL-6、TNF-α水平降低,结肠组织中p-ERK/ERK、p-p38 MAPK/p38 MAPK以及ERK、p38 MAPK mRNA表达显著降低(P<0.05),以上指标通路抑制剂组改善作用最显著.由此可得,雷公藤多苷可以有效改善溃疡性结肠炎炎症反应,促进结肠黏膜恢复,改善免疫功能,其机制可能与调控ERK/p38 MAPK信号通路有关.
Protective effect of Tripterygium glycosides on ulcerative colitis rats based on ERK/p38 MAPK signaling pathway
This study explored the effect of Tripterygium glycosides(TG)on ulcerative colitis in rats and examined the regulatory role of the extracellular signal-regulated kinase/p38 mitogen-activated protein kinase(ERK/p38 MAPK)signaling pathway.Seventy male Wistar rats were selected and randomly divided into control,model,low-dose TG,medium-dose TG,high-dose TG,positive control,and pathway inhibitor groups.The disease activity index(DAI)score,macroscopic damage score,and microscopic colonic injury score were observed in each group.HE staining was used to detect pathological changes in colonic tissues.TUNEL assay was employed to detect the apoptosis rate of intestinal mucosal cells.ELISA was used to measure serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α).Western blot and PCR methods were used to detect the expression of ERK/p38 MAPK pathway-related proteins and mRNA in tissues.The results showed that TG could effectively improve the histopathological condition;compared with the control group,DAI score,morphological injury score,colon injury score,apoptosis rate of colonic mucosal cells,serum levels of IL-1β,IL-6 and TNF-α,protein levels of p-ERK/ERK and p-p38 MAPK/p38 MAPK,mRNA levels of ERK and p38 MAPK were significantly elevated and significantly increased in the model group(P<0.05).Compared with the model group,DAI scores of rats in the high dose group of TG,the positive control group and the pathway inhibitor group were reduced,and the pathway inhibitor group was the lowest(P<0.05).Compared with the model group,morphological injury score and colonic injury score were reduced in the remaining groups,and lowest in the pathway inhibitor group(P<0.05).Compared with the model group,the apoptosis rate of rat intestinal mucosa cells was decreased in the high-dose TG,the positive control group,and the pathway inhibitor group,and the levels of IL-1β,IL-6,and TNF-α in serum,and the expression of p-ERK/ERK,p-p38 MAPK/p38 MAPK,ERK mRNA,p38 MAPK mRNA in the colonic tissues was reduced(P<0.05),and the improvement effect of the above indexes in the pathway inhibitor group was most significant.In conclusion,TG can effectively improve inflammatory responses in ulcerative colitis,promote colonic mucosal recovery,and enhance immune function.Its mechanism may be related to the regulation of the ERK/p38 MAPK signaling pathway.

ERK/p38 MAPK signaling pathwayTripterygium glycosidesulcerative colitis

肖慧荣、马慧群、吴成成

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江西中医药大学,江西 南昌 330004

江西中医药大学附属医院,江西 南昌 330006

ERK/p38 MAPK信号通路 雷公藤多苷 溃疡性结肠炎

江西省中医药管理局科技计划项目江西省教育厅课题

2023Z005GJJ190679

2024

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子:1.718
ISSN:1001-5302
年,卷(期):2024.49(19)