摘要
目的探讨健脾祛湿膏对肝郁脾虚型腹泻型肠易激综合征(IBS-D)大鼠的作用及其机制。方法参照三因素法(母婴分离+醋酸刺激+束缚应激)复制肝郁脾虚型IBS-D模型,随机将大鼠分为空白组,模型组,补脾益肠丸组,匹维溴铵组,健脾祛湿膏低、高剂量组。连续灌胃给药14 d后,评价各组大鼠粪便含水率、肠道疼痛阈值及糖水偏好值。取材后,检测各组结肠组织5羟色胺1A受体(5-HT1A)、5-HT2A受体、肿瘤坏死因子α(TNF-α)mRNA表达,闭锁小带蛋白1(ZO-1)、紧密连接蛋白-1(Claudin-1)和环状鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子(cGAS-STING)信号通路相关靶点mRNA及蛋白表达。结果与模型组比较,健脾祛湿膏组粪便含水率降低(P<0.05,P<0.01),肠道疼痛阈值和糖水偏好值升高(P<0.05,P<0.01),结肠组织干扰素β(IFN-β)水平、5-HT1A、5-HT2A、TNF-α、cGAS、STING mRNA和STING、TANK结合激酶1(TBK1)、p-TBK1蛋白表达降低(P<0.05,P<0.01),ZO-1、Claudin-1 mRNA和蛋白表达升高(P<0.05,P<0.01)。结论健脾祛湿膏能改善IBS-D大鼠症状,其作用机制可能与改善内脏高敏感、调节紧密连接蛋白表达、调控cGAS-STING通路激活相关。
AIM To investigate the effects and mechanism of Jianpi Qushi Paste on diarrhea-predominant irritable bowel syndrome(IBS-D)in rats with Liver Depression and Spleen Deficiency.METHODS The IBS-D model of Liver Depression and Spleen Deficiency was reproduced with intervention of the three causative factors of mother-infant separation,acetic acid stimulation,and restraint stress.The rats were randomly divided into the blank group,the model group,Bupi Yichang Pills group,pinaverium bromide group,and the low dose and high dose Jianpi Qushi Paste groups.After 14 days consecutive corresponding gavage,the rats of each group had their fecal water content,intestinal pain threshold and sugar water preference evaluated.After the procurement of tissue samples,the rats of each group had their colon tissues levels of mRNA expressions of serotonin 1A and 2A receptor(5-HT1A and 5-HT2A),tumor necrosis factorα(TNF-α),mRNA and protein expressions of zona atresia protein 1(ZO-1),claudin-1 and cyclic guanosine-adenylate synthetase-interferon gene stimulating targets(cGAS-STING)detected.RESULTS Compared with the model group,Jianpi Qushi Paste groups displayed decreased water content of feces(P<0.05,P<0.01);increased threshold of intestinal pain and preference value of sugar water(P<0.05,P<0.01);decreased interferonβ(IFN-β)level,expressions of 5-HT1A,5-HT2A,TNF-α,cGAS,STING mRNA,and STING,TANK-binding kinase 1(TBK1),p-TBK1 proteins in colon tissue(P<0.05,P<0.01),and decreased mRNA and protein expressions of ZO-1 and Claudin-1(P<0.05,P<0.01).CONCLUSION Jianpi Qushi Paste can improve the symptoms of IBS-D rats,and its mechanism may be related to the improvement of visceral hypersensitivity,expression of tight junction protein,and the activation of cGAS-STING pathway.
作者
谢翔雨
卢琴
甘剑峰
卢淑婷
熊维
杨惠霏
何国栋
黄育生
唐洪梅
XIE Xiang-yu;LU Qin;GAN Jian-feng;LU Shu-ting;XIONG Wei;YANG Hui-fei;HE Guo-dong;HUANG Yu-sheng;TANG Hong-mei(The First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510120,China;Artemisia annua Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Hospital Affiliated to Guangzhou University of Chinese Medicine,Guangzhou 510405,China)
出处
《中成药》
CAS
CSCD
北大核心
2023年第9期2875-2882,共8页
Chinese Traditional Patent Medicine
基金
广东省自然科学基金项目(2019A1515011745)
广东省中医药管理局科研项目(20203013)
广东省医院协会药学科研专项基金(恒瑞)项目(2021YXZD02)
广州中医药大学第一附属医院高水平医院建设临床研究专项项目(211010010708)。
关键词
健脾祛湿膏
肝郁脾虚型腹泻型肠易激综合征
肠道低度炎症
cGAS-STING信号通路
紧密连接蛋白
Jianpi Qushi Paste
diarrhea-predominant irritable bowel syndrome with Liver Depression and Spleen Deficiency
low-grade intestinal inflammation
cGAS-STING signaling pathway
tight junction proteins