香连化浊方对慢性萎缩性胃炎模型大鼠胃黏膜EGFR/MAPK/ERK信号通路的影响  

Effect of Xianglian Huazhuo Formula(香连化浊方)on EGFR/MAPK/ERK Signaling Pathway in Gastric Mucosa in Chronic A trophic Gastritis Model Rats

作　　者：杨玥玮 程楠 刘丽然 董佳琪 柳亚杰 姜建明 杨倩[3] 李博林 YANG Yuewei;CHENG Nan;LIU Liran;DONG Jiaqi;LIU Yajie;JIANG Jianming;YANG Qian;LI Bolin(Graduate School,Hebei University of Chinese Medicine,Shijiazhuang,05009l;Hebei University of Chinese Medicine;Hebei Provincial Hospital of Traditional Chinese Medicine)

机构地区：[1]河北中医学院研究生院,河北石家庄050091 [2]河北中医学院 [3]河北省中医院

出　　处：《中医杂志》2023年第14期1483-1490,共8页Journal of Traditional Chinese Medicine

基　　金：国家中医临床研究基地建设项目(国中医药科技函[2018]131号);国家科技部重点研发课题(2018YFC1704102);河北省重点研发计划(21377724D,21377740D);河北省中医药管理局科研计划(2022026)。

摘　　要：目的 探讨香连化浊方治疗慢性萎缩性胃炎(CAG)的可能作用机制。方法 利用GEO数据库筛选出基因芯片数据集,基于GEO2R工具、GeneCards数据库获得CAG增殖相关差异基因。采用Metascape平台对CAG增殖相关差异基因进行GO分析和KEGG富集分析,寻找与CAG相关的生物过程及重要信号通路,并进行动物实验验证。70只Wistar大鼠,随机抽取14只作为正常组进行常规饲养,其余56只大鼠采用“N-甲基-N’-硝基-亚硝基胍+饥饱失常+水杨酸钠”联合造模法制备CAG模型。造模成功的50只大鼠随机分为模型组、摩罗丹组和香连化浊方低、中、高剂量组,每组10只。摩罗丹组大鼠给予摩罗丹溶液1.4 g/(kg·d)灌胃,香连化浊方高、中、低剂量组大鼠分别给予香连化浊方溶液36、18、9 g/(kg·d)灌胃,正常组和模型组大鼠给予生理盐水0.01 ml/g灌胃,各组均每日1次,连续60天。HE法观察大鼠胃黏膜组织病理学变化,透射电镜观察大鼠胃黏膜细胞超微结构,Western-blot法检测胃黏膜组织中表皮生长因子受体(EGFR)、磷酸化细胞外信号调节蛋白激酶1 (p-ERK1)、原癌基因(c-myc)蛋白表达水平,RT-PCR法检测胃黏膜组织EGFR、细胞外信号调节蛋白激酶1 (ERK1)、c-myc mRNA表达。结果 最终得到45个CAG增殖相关差异基因。GO和KEGG富集分析结果显示,可影响正向调控细胞因子的产生、正向调控丝裂原活化蛋白激酶(MAPK)级联反应、调节氧化应激诱导的细胞死亡等,涉及与癌症通路、MAPK信号通路、辅助性T细胞17(Th17)细胞分化等多个信号通路。HE染色可见各给药组大鼠胃黏膜厚度、固有层腺体排列状态、炎性细胞浸润情况等方面较模型组均有改善,其中以香连化浊方高、中剂量组效果最佳。透射电镜结果显示,与模型组比较,各药物干预后,线粒体结构恢复,内质网肿胀减轻,以香连化浊方高、中剂量组效果较为显著。与正常组比较,模型组大�Objective To explore the potential mechanism of Xianglian Huazhuo Formula(香连化浊方,XHF)in the treatment of chronic atrophic gastritis(CAG).Methods The gene chip dataset was screened out by using the CEO database,and the CAG proliferation-related differential genes were obtained based on the GEO2R tool and GeneCards database.The Metascape platform was used to perform GO and KEGG enrichment of CAG proli-ferationrelated differential genes so as to find biological processes and important signaling pathways related to CAG,and conduct animal experiments to verify.From 70 Wistar rats,14 rats were randomly selected as the normal group for routine feeding,and the remaining 56 rats were given"N-methyl-N'-nitro-nitrosoguanidine plus disordered feeding plus sodium salicylate"to prepare the CAG model.The 50 successfully modeled rats were randomly divided into model group,morodan group,and XHF high-,medium-and low-dose groups,with 10 rats in each group.The rats in the morodan group were given 1.4 g/(kg d)of morodan solution by gavage,while those in the high-,medium-and low-dose XHF groups were given 36,18 and 9 g/(kg d)of XHF solution by gavage,respectively,and the rats in the normal group and the model group were given O.01 ml/g of normal saline by gavage,once a day,for 60 consecutive days.HE was used to observe the histopathological changes of the gastric mucosa of rats,and transmitted electron microscopy was taken to observe the ultrastructure of gastric mucosal cells.The protein expression levels of epidermal growth factor receptor(EGFR),phosphorylated extracellular signal-regulated protein kinase 1(p-ERK1)and proto-oncogene(c-myc)were detected by Western-blot,and the mRNA expression levels of EGFR,extracellular signal-regulated protein kinase 1(EPK1)and c-myc were detected by RT-PCR method.Results Finally,45 CAG proliferationrelated differential genes were obtained.CO and KEGG enrichment analysis showed that it could affect the positive regulation of cytokine production,positive regulation of mitogen-activated prot

关 键 词：慢性萎缩性胃炎 香连化浊方 表皮生长因子受体 丝裂原活化蛋白激酶 细胞外信号调节蛋白激酶 

分 类 号：R285.5[医药卫生—中药学]