清化饮对慢性胃炎脾胃湿热证模型大鼠miR155/SOCS1介导的炎症通路的作用机制研究

王薇 徐丛荣 任彦 王施玮 廖春丽 付肖岩 胡海霞

摘要：目的基于miR-155/SOCS1炎癥通路研究清化饮对慢性胃炎脾胃湿热证治疗作用的机制研究。方法将60只Wistar大鼠随机分为对照组、脾胃湿热模型组、清化饮组，采用湿热环境+高脂高糖饮食+白酒的造模方法建立脾胃湿热证慢性胃炎大鼠模型，清化饮连续灌胃给药20 d。治疗结束后处死大鼠，腹主动脉取血并留取胃组织，HE染色观察胃组织病理改变情况，应用ELISA检测血清TNF-α、IL-6的含量，应用RT-PCR法检测miR-155及其靶基因SOCS1的表达水平，应用免疫组化实验检测转录因子NFκB p65及SOCS1的蛋白表达水平。结果与对照组比较，脾胃湿热模型组大鼠胃组织炎症细胞浸润增多，且miR-155的表达量明显上调，其靶基因SOCS1显著下调，导致炎症通路关键的转录因子NFκB p65核内表达水平及血清TNF-α、IL-6的生成显著上升。而与模型组比较，清化饮可降低胃组织炎症细胞的浸润和miR-155的表达水平，并且使NFκB p65的核内表达水平降低，同时上调SOCS1表达，进而降低TNF-α、IL-6的分泌水平。结论清化饮可通过miR-155/SOCS1通路抑制NFκB活化及过度炎症反应保护胃组织，为临床治疗慢性胃炎脾胃湿热证提供基础理论依据。

关键词：清化饮;慢性胃炎;脾胃湿热模型;miR-155;炎症通路.

The study of regulation of Qinghuayin on the rat model of spleen stomach damp heat syndrome of chronic gastritis via miR-155/SOCS1 mediated inflammatory pathway

Wang Wei1，Xu Congrong1，Ren Yan1，Wang Shiwei1，Fu Xiaoyan1，Liao Chunli1，Hu Haixia2，3

1 The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine，Fuzhou，Fujian，350003，China

2 Academy of Integrative Medicine，Fujian University of Traditional Chinese Medicine，Fuzhou，Fujian 350122，China

3 Fujian Key Laboratory of Integrative Medicine on Geriatrics，Fujian University of Traditional Chinese Medicine，Fuzhou，Fujian 350122，China

Abstract：Objective To study the therapeutic mechanism of Qinghuayin on spleen and stomach dampness-heat syndrome of chronic gastritis via miR-155/SOCS1 mediated inflammatory pathway.Methods 60 Wistar rats were randomly divided into control group，spleen stomach damp heat model group and Qinghuayin group.The wet heat environment plus a high-fat and high-sugar diet was used to establish a rat model of dampness-heat syndrome of the spleen and stomach，and Qinghuayin was continuously intragastric administered for 20 days.After treatment，the rats were executed and then the blood of abdominal aorta was taken and the gastric tissue was retained for analysis.HE staining was used to observe the pathological changes of gastric tissue，the serum TNF-αand IL-6 was detected by ELISA.The expression level of miR-155 and its target gene SOCS1 was detected by RT-PCR，the protein expression levels of NFκB p65 and SOCS1were detected by immunohistochemistry.Results Compared with the control group，the infiltration of inflammatory cells were increased significantly in gastric tissue of rats with dampness-heat syndrome of the spleen and stomach model group，the expression of miR-155 was significantly up-regulated，and its target gene SOCS1 was significantly down regulated，resulting in the increased expression level of transcription factor NFκB p65 in nucleus and SOCS1，and the production of TNF-αand IL-6 increased significantly in rat serum.However，Qinghuayin can reduce the infiltration of inflammatory cells and the expression level of miR-155 in gastric tissue，and reduce the nuclear expression level of NFκB p65 decreased，up-regulated the expression of SOCS1，thereby reducing the secretion level TNF-αand IL-6 comparing with model group.Conclusion Qinghuayin can inhibit NFκB activation through miR-155/SOCS1 pathway and excessive inflammatory reaction，protecting gastric tissue from damage and providing basic theoretical basis for clinical treatment of spleen and stomach dampness-heat syndrome of chronic gastritis.

Key words：Qinghuayin;Chronic gastritis;spleen and stomach dampness-heat syndrome;miR-155;Inflammatory pathway

【中图分类号】R573  【文献标识码】A  【文章编号】1673-9026（2021）14--03

慢性胃炎病症表现为纳差、嘈杂、烧心等症状，在中医划归为“胃脘痛”“痞满”等疾病范畴，其临床治疗目前无特效药物，长期使用西医治疗会造成耐药，治疗效果不佳且易复发。慢性胃炎发病多会累及脾，脾胃湿热是其最为常见的证型[1，2]。……