基于外泌体探讨电针对功能性消化不良大鼠十二指肠炎症及IKK/NF-κB信号通路的影响  

Exosome-Based Exploration of the Effects of Electroacupuncture on Duodenal Inflammation and IKK/NF-κB Signaling Pathway in Rats with Functional Dyspepsia

作　　者：崔冬梅 陈皖倩 康朝霞 CUI Dongmei;CHEN Wanqian;KANG Zhaoxia(Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550025,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025

出　　处：《中医药导报》2024年第12期38-43,52,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(82060897);贵州省科技计划项目(黔科合基础-ZK[2022]一般466);贵州省中医药管理局中医药、民族医药科学技术研究项目(QZYY-2022-007)。

摘　　要：目的:基于外泌体探讨电针对功能性消化不良(FD)大鼠十二指肠炎症及IKK/NF-κB信号通路相关蛋白的影响。方法:将50只SD大鼠随机分为空白组(10只)、造模组(40只)。造模组采用多因素造模方法制备FD模型。选择造模成功的30只大鼠随机分为模型组、电针组、抑制剂组,每组10只。电针组给予电针“足三里”穴干预14 d;抑制剂组给予外泌体抑制剂GW4869(1.25μg/g)腹腔注射,每2天1次,共7次。干预结束后比较各组大鼠十二指肠组织超微结构、外泌体浓度及粒径大小、闭合蛋白-1、闭合小环蛋白-1及外泌体表面标志蛋白CD81的分布表达情况及炎症因子TNF-α、IKKα、p-IKKα、NF-κB p65、p-NF-κB p65的表达情况。结果:透射电镜结果显示,与空白组比较,模型组大鼠十二指肠细胞间隙增大,链接结构模糊,细胞内线粒体、内质网等超微结构紊乱,线粒体结构损伤明显,嵴紊乱、断裂甚至溶解消失,线粒体增多,明显缩小,其内染色深,萎缩。电针及抑制剂干预后,大鼠十二指肠细胞形态较模型组好转。与模型组比较,电针组、抑制剂组大鼠十二指肠组织闭合蛋白-1、闭合小环蛋白-1表达显著增加(P<0.01);与模型组比较,电针组、抑制剂组大鼠十二指肠组织中外泌体表面标志蛋白CD81平均光密度值显著降低(P<0.01);与模型组比较,电针组、抑制剂组大鼠十二指肠组织TNF-α、IKKα、p-IKKα、NF-κB p65、p-NF-κB p65蛋白表达降低(P<0.01)。结论:在炎症状态下,电针和外泌体抑制剂均可以抑制FD大鼠十二指肠组织中外泌体的释放,抑制炎症因子TNF-α、IKK/NF-κB炎症通路的激活,改善肠道炎症。其可能通过抑制TNF-α/IKKα/p-IKKα/NF-κB p65/p-NF-κB p65通路相关蛋白表达发挥作用。Objective:To explore the effects of electroacupuncture on duodenal inflammation and IKK/NF-κB signaling pathway-related proteins in functional dyspepsia(FD) rats based on exosomes.Methods:Totally 50 SD rats were randomly divided into blank group(10 rats) and modeling group(40 rats).In the modeling group,a multifactorial modeling method was used to prepare the FD model.A total of 30 rats with successful modeling were randomly divided into model group,electroacupuncture group and inhibitor group,with 10 rats in each group.In the electroacupuncture group,electroacupuncture was applied to the "Zusanli"(ST 36) for 14 days.In the inhibitor group,the exosome inhibitor GW4869(1.25 μg/g) was injected intraperitoneally once every 2 days for a total of 7 times.At the end of the intervention,the ultrastructure of duodenal tissue,exosomes concentration and particle size,occludin-1,zonula occludin-1,CD81,as well as the protein expression of TNF-α,IKK α,p-IKK α,NF-κB p65,and p-NF-κB p65 were compared among the groups.Results:The results of transmission electron microscopy showed that compared with the blank group,the duodenal cell gap increased in model group,and that the linkage structure was blurred;The intracellular mitochondria,endoplasmic reticulum and other superworldly structures were disorganized in model group,and the mitochondrial structure was obviously damaged;The cristae were disorganized,fractured or even lysed and disappeared in model group,and the mitochondria were increased and obviously narrowed;The staining within them was deep and atrophic in mod el group.After the intervention of electroacupuncture and inhibitors,the morphology of rat duodenal cells was better than that of the model group.Compared with the model group,there was a significant increase in the expression of occludin-1 and zonula occludin-1 in duodenal tissues in electroacupuncture group and inhibitor group(P<0.01);Compared with the model group,the average optical density value of CD81 in duodenal tissues decreased in electroacupuncture

关 键 词：功能性消化不良 电针 十二指肠炎症 外泌体 IKK/NF-κB信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]