舒胃汤调节PI3K/AKT信号通路抑制功能性消化不良大鼠ICCs凋亡  

Shuwei Decoction Inhibits ICCs in Rats with Functional Dyspepsia via Regulating PI3K/AKT Signaling Pathway

作　　者：梁俊尧 郭璇[1] 周韬 张德旭 徐寅[1] LIANG Jun-yao;GUO Xuan;ZHOU Tao;ZHANG De-xu;XU Yin(Department of Gastroenterology,The First Hospital of Hunan University of Chinese Medicine,Changsha 410000)

机构地区：[1]湖南中医药大学第一附属医院脾胃病科,长沙410000

出　　处：《中国中西医结合杂志》2025年第2期198-204,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金项目(No.81904176);湖南省自然科学基金(No.2023JJ60044);湖南创新型省份建设专项项目(No.21B0389);湖南省中医药科研课题(No.B2023079);湖南省科技创新计划项目(No.2021SK51413)。

摘　　要：目的 基于磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)信号通路及胃窦Cajal间质细胞(ICCs)增殖探讨舒胃汤对功能性消化不良(FD)肝郁脾虚证大鼠的作用机制。方法 将40只SD大鼠按随机数字表法分为空白组、模型组、舒胃汤组(7.56 g/kg)、莫沙必利组(1.35×10^(-3) g/kg),每组10只。除空白组外,其余组采用改良复合病因造模(慢性束缚应激+夹尾激怒+过度疲劳+饮食失节)制备FD肝郁脾虚证模型大鼠。造模21天后,空白组与模型组给予生理盐水灌胃,舒胃汤组和莫沙必利组给予对应药物灌胃,持续14天。检测大鼠体重、胃排空率及小肠推进率;高架十字迷宫实验观察大鼠行为学变化;HE染色法观察胃窦组织损伤情况;Western Blot检测PI3K、AKT、钙离子激活的氯离子通道蛋白(ANO1)蛋白表达水平;RT-qPCR检测大鼠胃窦PI3K、p-AKT、ANO1 mRNA表达水平;免疫组织荧光共定位法检测c-kit表达水平;CCK8检测ICCs增殖水平;流式细胞仪检测ICCs凋亡水平。结果 与空白组比较,模型组大鼠体重、小肠推进率、胃排空率下降,PI3K、p-AKT、ANO1蛋白及mRNA表达水平下降(P<0.05),c-kit表达及ICCs增殖水平下降(P<0.05),凋亡水平上升(P<0.05)。与模型组比较,舒胃汤组及莫沙必利组大鼠体重、小肠推进率、胃排空率上升,PI3K、p-AKT、ANO1蛋白及mRNA表达上升(P<0.05),c-kit表达及ICCs增殖水平上升(P<0.05),凋亡水平下降(P<0.05)。结论 舒胃汤可升高FD肝郁脾虚证大鼠胃排空率和小肠推进率,减少ICC及胃窦细胞凋亡,改善FD胃肠运动,其作用机制可能与PI3K/AKT信号通路调控ICCs有关。Objective To explore the mechanism of Shuwei Decoction(SWD) on functional dyspepsia(FD) rats with Gan stagnation and Pi deficiency syndrome(GSPDS) based on PI3K/AKT signaling pathway and the proliferation of Cajal interstitial cells(ICCs) in gastric antrum. Methods Forty SD rats were divided into the control group, model group, SWD group(7.56 g/kg), and Mosapride group(1.35×10^(-3) g/kg) using a random number table,with 10 rats in each group. Except those in the control group, FD rats with GSPDS in the remaining groups were established using an enhanced composite etiology model(encompassing chronic restraint stress, tail-clamping, excessive fatigue, and dietary disturbances). After 21 days of modeling, rats in the control and the model groups were given normal saline by gavage, rats in the SWD and Mosapride group were administered with the corresponding drugs by gavage for 14 days. Body weight changes, gastric emptying rate and small intestinal propulsive rate were detected. Behavioral changes were evaluated using the elevated plus-maze test. The pathological injury degrees of gastric antral tissue was observed by HE staining, and the protein expression levels of phosphatidyli-nositol-3 kinase(PI3K), protein kinase B(AKT), p-AKT, and anoctamin-1(ANO1)were detected by Western Blot. Additionally, the mRNA expression levels of PI3K, p-AKT, and ANO1 were detected in gastric sinus using RT-qPCR. The c-kit expression level was detected by immunofluorescence colocalization, while the proliferative activity of ICCs was evaluated with CCK8, along with apoptosis rate of ICCs was measured by flow cytometry. Results Compared with the control group,the model group exhibited a decrease in body weight,gastric emptying rate, and small intestinal propulsive rate, as well as a decrease in proteins and mRNA expression levels of PI3K, p-AKT, ANO1(P<0.05),a decrease in the expression of c-kit and proliferative rate of ICCs(P<0.05), and an increase in level of apoptosis(P<0.05).Compared with the model group,the SWD and Mosapride grou

关 键 词：功能性消化不良 舒胃汤 磷脂酰肌醇-3激酶/蛋白激酶B信号通路 氯离子通道蛋白 CAJAL间质细胞 中药复方 中西医结合 

分 类 号：R285.5[医药卫生—中药学]