香连化浊方对慢性萎缩性胃炎大鼠凋亡信号通路相关因子的影响  

Effects of Xianglian Huazhuo Recipe on apoptosis signal pathway related factors in rats with chronic atrophic gastritis

作　　者：高云霄 王杰[1] 马虹宇[2] 贾雪梅 郭榆西 李博林[3,4] 杨倩 GAO Yun-xiao;WANG Jie;MA Hong-yu;JIA Xue-mei;GUO Yu-xi;LI Bo-lin;YANG Qian(Graduate School of Hebei University of Chinese Medicine,Shijiazhuang 050091,China;Hebei General Hospital,Shijiazhuang 050051,China;Hebei Provincial Hospital of Traditional Chinese Medicine,Shij iazhuang 050011,China;Hebei Key Laboratory of Gastroenterology Research of Integrated Traditional Chinese and Western Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北中医学院研究生院,石家庄050091 [2]河北省人民医院,石家庄050051 [3]河北省中医院,石家庄050011 [4]河北省中西医结合胃肠病研究重点实验室,石家庄050011

出　　处：《中华中医药杂志》2023年第3期1050-1057,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家中医临床研究基地建设项目(No.国中医药办科技函〔2018〕131号);国家重点研发计划(No.2018YFC1704100,No.2018YFC1704102);河北省省级科技计划资助(No.21377724D,No.21377740D);河北省中医药管理局科研计划项目(No.2021034,No.2022026,No.2022032)。

摘　　要：目的:基于基因表达综合数据库(GEO)和GeneCards两大数据库筛选慢性萎缩性胃炎(CAG)凋亡相关重要靶点,并通过动物实验探讨香连化浊方对其的影响。方法:利用GEO数据库下载关于CAG的芯片数据,应用GEO2R在线工具进行差异表达分析;利用GeneCards数据库获取凋亡相关基因;采用Venny 2.1.0软件得出CAG凋亡相关差异基因,进行生物信息学分析,进而确定凋亡通路上的重要靶点;通过综合造模法复制CAG大鼠模型,将造模成功的50只大鼠按随机数表法分为模型组,摩罗丹组,香连化浊方低、中、高剂量组,每组10只,同时另设正常组10只;用RT-qPCR法检测各组大鼠胃黏膜c-Jun氨基末端激酶(JNK)1、有丝分裂原活化蛋白激酶1(MAPK1)mRNA的表达,免疫组化法检测各组大鼠胃黏膜P53、Fas蛋白的表达。结果:通过GEO2R在线工具筛选得出744个CAG差异基因,利用GeneCards数据库搜索共得出405个凋亡相关基因,取二者交集的17个CAG凋亡相关差异基因进行生物信息学分析,发现JNK1、MAPK1、P53、Fas为凋亡通路上的重要靶点。动物实验结果示:与正常组比较,模型组大鼠胃黏膜组织中JNK1、MAPK1 mRNA和P53蛋白表达显著升高(P<0.01),Fas蛋白表达显著降低(P<0.01);与模型组比较,各药物组胃黏膜组织中JNK1、MAPK1 mRNA表达显著降低(P<0.05,P<0.01),摩罗丹组与香连化浊方高、中剂量组胃黏膜组织中P53蛋白表达显著降低(P<0.01),而Fas蛋白表达显著升高(P<0.05,P<0.01);与摩罗丹组比较,香连化浊方高剂量组胃黏膜组织中JNK1、MAPK1 mRNA和P53蛋白表达显著降低(P<0.01,P<0.05),而Fas蛋白表达则显著升高(P<0.01),香连化浊方中剂量组胃黏膜组织中JNK1 mRNA表达显著降低(P<0.05)。结论:香连化浊方能够明显改善CAG大鼠胃黏膜萎缩,其作用机制可能是通过降低MAPK1 mRNA表达,激活CAG大鼠胃黏膜细胞凋亡信号传导通路,降低JNK1 mRNA、P53蛋白表达,升高Fas蛋白表达,从而促进�Objective:Based on gene expression omnibus(GEO)and genecards,we screened the important targets related to apoptosis in chronic atrophic gastritis(CAG),and discussed the effects of Xianglian Huazhuo Recipe on it through animal experiments.Methods:The chip data about CAG was downloaded by GEO database,and the differential expression analysis was carried out by GEO2R online tool;The apoptosis related genes were obtained by GeneCards database;The differential genes related to CAG apoptosis were obtained by Venny 2.1.0 software,and the important targets on the apoptosis pathway were determined by bioinformatics analysis;The CAG rat model was duplicated by the comprehensive modeling method.The 50 rats that were successfully modeled were divided into model group,morodan group,low,medium and high dose groups of Xianglian Huazhuo Recipe,with 10 rats in each group,and 10 rats in the normal group;The expression of c-Jun N-terminal kinase(JNK)1 and mitogen activated protein kinase1(MAPK1)mRNA in gastric mucosa of rats in each group was detected by RT-qPCR,and the expression of P53 and Fas protein in gastric mucosa of rats in each group was detected by immunohistochemistry.Results:A total of 744 CAG differential genes were screened by GEO2R online tool,and 405 apoptosis related genes were searched by GeneCards database.The 17 CAG apoptosis related differential genes intersected by the two were analyzed by bioinformatics.It was found that JNK1,MAPK1,P53 and Fas were important targets in the apoptosis pathway.The results of animal experiment showed that compared with the normal group,the expression of JNK1,MAPK1 mRNA and P53 protein in the gastric mucosa of the model group was significantly increased(P<0.01),while the expression of Fas protein was significantly decreased(P<0.01);Compared with the model group,the expression of JNK1 and MAPK1 mRNA in gastric mucosa tissue of each drug group was significantly decreased(P<0.05,P<0.01),the expression of P53 protein in gastric mucosa tissue of morodan group and high and medium dose g

关 键 词：香连化浊方 慢性萎缩性胃炎 生物信息学 JNK1 MAPK1 P53 FAS 

分 类 号：R285.5[医药卫生—中药学]