基于TMT定量蛋白质组学探讨半夏泻心汤治疗慢性萎缩性胃炎大鼠的作用机制  

Exploring the action mechanism of Banxia Xiexin Decoction in treating rats with chronic atrophic gastritis based on TMT quantitative proteomics

作　　者：张馨元 马佳乐 吕亚龙[3] 李慧臻[2] ZHANG Xin-yuan;MA Jia-le;LV Ya-long;LI Hui-zhen(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China;Anguo Municipal Hospital of Traditional Chinese Medicine,Anguo 071200,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津中医药大学第二附属医院,天津300250 [3]安国市中医院,河北安国071200

出　　处：《时珍国医国药》2025年第4期795-800,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(822274442)。

摘　　要：目的运用串联质谱标签(TMT)定量蛋白质组学技术,揭示半夏泻心汤治疗慢性萎缩性胃炎(CAG)大鼠模型的作用机制。方法从36只SPF级SD雄性大鼠中随机选取10只作为空白组(n=10)正常饲养,其余26只模拟胃酸减少、烫热高盐及不规律饮食造成CAG大鼠模型,造模完成后将剩余大鼠随机分为模型组(n=12)及半夏泻心汤组(n=11),半夏泻心汤组用10ml/kg,1次/日剂量的半夏泻心汤灌胃,空白组和模型组给予等量生理盐水,干预12周后取大鼠胃组织,通过苏木素-伊红(HE)染色观察胃病理组织学情况,通过TMT组学技术分析各组之间差异蛋白,取交集差异蛋白进行功能富集分析,并采用蛋白免疫印迹法(Western blot)验证最显著的差异蛋白Vdac3及Cryz的表达。结果半夏泻心汤能改善CAG大鼠胃组织的病理状态。蛋白质组学结果显示,根据差异倍数及P值,对照组、模型组与模型组、半夏泻心汤组的交集差异蛋白共有22种,根据logFC值,Vdac3、Cryz是其中表达量差异最大的两种蛋白。富集分析结果显示,半夏泻心汤治疗CAG的机制可能涉及肥厚型心肌病、ROS信号通路、PPAR信号通路等通路;肌节组织、肌肉收缩等生物学过程;肌小节z线、肌小节m带等细胞组成;Ankyrin蛋白结合、NADPH结合等分子功能。Western blot结果显示,半夏泻心汤能显著提高CAG大鼠的Vdac3表达,降低Cryz表达(P<0.05)。结论半夏泻心汤能显著改善CAG大鼠胃组织病理情况,可能与提高Vdac3、降低Cryz表达有关,通过多途径、多靶点发挥作用。Objective To elucidate the mechanism of Banxia Xiexin Decoction(BXD)in treating chronic atrophic gastritis(CAG)in a rat model using tandem mass tag(TMT)quantitative proteomics.Methods Ten out of 36 SPF-grade male SD rats were randomly as⁃signed as the blank group(n=10)and raised normally,while the remaining 26 rats were used to establish the CAG rat model by reduc⁃ing gastric acid,scalding with high salt and giving irregular diet.After modeling,the remaining rats were randomly divided into the mod⁃el group(n=12)and the BXD group(n=11).The BXD group was intragastrically administered with BXD at a dose of 10ml/kg/d while the blank group and model group were given an equal amount of normal saline.After 12 weeks of intervention,the gastric tissues were obtained from the rats.Hematoxylin-eosin(HE)staining was performed to observe the histopathological changes in the gastric tis⁃sues.The differential proteins between groups were analyzed using TMT proteomics.Functional enrichment analysis was conducted on the intersection differential proteins,and the expressions of the most significant differential proteins,Vdac3 and Cryz,were validated using Western blot(WB).Results BXD improved the pathological conditions of the gastric tissues in CAG rats.Based on the fold change and P-values,proteomics results showed that there were 22 common differential proteins between the control vs.model group and the model vs.BXD group.According to logFC values,Vdac3 and Cryz were the two proteins with the largest differences in expression.Enrichment analysis suggested that the mechanism of BXD in treating CAG might involve pathways such as hypertrophic cardiomyopathy,ROS signa⁃ling pathway,and PPAR signaling pathway;biological processes such as sarcomere organization and muscle contraction;cellular compo⁃nents such as sarcomere Z disc and M band;molecular functions such as Ankyrin binding and NADPH binding.WB results demonstrated that BXD significantly increased the expression of Vdac3 and decreased the expression of Cryz in CAG

关 键 词：半夏泻心汤 慢性萎缩性胃炎 蛋白质组学 串联质谱标签 

分 类 号：R285.5[医药卫生—中药学]