芍药甘草汤调控ASIC3/ERK信号通路改善慢传输型便秘大鼠肠道动力的机制研究
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篇名: 芍药甘草汤调控ASIC3/ERK信号通路改善慢传输型便秘大鼠肠道动力的机制研究
TITLE: Study on the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation by regulating the ASIC3/ERK signaling pathway
摘要: 目的 探讨芍药甘草汤调控酸敏感离子通道3(ASIC3)/胞外信号调节激酶(ERK)信号通路改善慢传输型便秘(STC)大鼠肠道动力的作用机制。方法SD大鼠采用复方地芬诺酯灌胃构建STC模型,将造模成功大鼠随机分为模型组、芍药甘草汤组(1.5g/mL)、乳果糖组(208.4mg/mL,阳性对照)、联合抑制组(芍药甘草汤1.5g/mL+盐酸阿米洛利20μg/kg),每组12只,另取12只健康大鼠作为空白组;每天给药1次,连续干预14d。干预完成后检测大鼠肠道传输功能、内脏敏感性,采用免疫组化染色观察大鼠结肠组织中ASIC3的表达,检测大鼠结肠组织中ASIC3、ERK1、ERK2mRNA的表达和ASIC3、ERK1/2、磷酸化ERK1/2(p-ERK1/2)蛋白的表达;观察大鼠结肠肠神经调节系统(ENS)-Cajal间质细胞(ICC)-平滑肌细胞(SMC)网络超微结构变化。结果与模型组比较,芍药甘草汤组大鼠肠道推进率显著升高,内脏痛阈值显著降低,结肠组织中ASIC3阳性面积占比显著升高,结肠组织中ERK1、ERK2、ASIC3mRNA相对表达量和p-ERK1/2、ASIC3蛋白相对表达量以及p-ERK1/2与ERK1/2比值均显著升高(P<0.05或P<0.01);ICC、SMC形态结构明显修复,缝隙连接更加紧密。与芍药甘草汤组比较,联合抑制组大鼠肠道动力的改善效果减弱,部分指标水平差异有统计学意义(P<0.05或P<0.01);ICC、SMC形态结构的修复作用明显减弱。结论芍药甘草汤可有效改善STC大鼠肠道传输功能并促进肠道修复,其作用机制可能与调控ASIC3/ERK信号通路介导ENS-ICC-SMC网络从而改善肠道动力、降低内脏敏感性有关。
ABSTRACT: OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation (STC) by regulating acid-sensitive ion channel 3 (ASIC3)/extracellular signal-regulated kinase (ERK) signaling pathway. METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate. The successfully modeled rats were randomly divided into model group, Shaoyao gancao decoction group (1.5 g/mL), lactulose group (208.4 mg/mL, positive control), and combined inhibition group (Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg), with 12 rats in each group. Additionally, 12 healthy rats were selected as the blank group. They were given relevant medicine once a day and continuously intervened for 14 days. After intervention, the intestinal propulsion function and visceral sensitivity of the model rats were detected. The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining. mRNA expressions of ASIC3, ERK1 and ERK2 as well as protein expressions of ASIC3, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in colon tissue of rats were detected; the ultrastructural changes of the enteric nervous system (ENS) -interstitial cell of Cajal (ICC)-smooth muscle cell (SMC) network in the rat colon were observed under electron microscopy. RESULTS Compared with the model group, the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased, while the visceral pain threshold was significantly decreased. The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased. The relative mRNA expression levels of ERK1, ERK2, and ASIC3, as well as the relative protein expression levels of p-ERK1/2 and ASIC3, and the p-ERK1/2 to ERK1/2 in the colonic tissue, were all significantly increased (P<0.05 or P<0.01). Additionally, there was marked repair of the morphological structure of ICC and SMC, with closer gap junctions observed. Compared with the Shaoyao gancao decoction group, the combined inhibition group exhibited a diminished improvement in intestinal motility of rats, with statistically significant differences in the levels of some indicators (P<0.05 or P<0.01); the repairing of the morphological structure of ICC and SMC was notably attenuated. CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats, and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway, thus promoting intestinal motility and reducing visceral sensitivity.
期刊: 2025年第36卷第15期
作者: 张紫麒;周鸿雲;赵琼;邓媛;赵梦洁;赵辰;陈静仪
AUTHORS: ZHANG Ziqi,ZHOU Hongyun,ZHAO Qiong,DENG Yuan,ZHAO Mengjie,ZHAO Chen,CHEN Jingyi
关键字: 慢传输型便秘;芍药甘草汤;酸敏感离子通道3;胞外信号调节激酶;ENS-ICC-SMC网络
KEYWORDS: slow transit constipation; Shaoyao gancao decoction; ASIC3; ERK; ENS-ICC-SMC network
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