摘要
目的观察电针对类风湿关节炎(RA)模型家兔肠道菌群及血清炎性因子的影响,探讨其治疗RA的作用机制。方法采用卵蛋白诱导联合完全弗氏佐剂建立RA家兔模型,将造模成功家兔随机分为模型组、益生菌组和电针组,每组6只,另取6只家兔作为正常组。电针组电针双侧“足三里”“犊鼻”,30 min/次,益生菌组予益生菌胶囊溶液(14.5 mg/kg)灌胃,均1次/d,连续2周。测量家兔膝关节周径、痛阈,HE染色观察结肠组织和滑膜组织病理形态,16S rDNA测序分析肠道菌群结构变化,ELISA检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6含量。结果与正常组比较,模型组家兔膝关节周径显著增加、痛阈显著降低(P<0.01);结肠黏膜损伤严重,杯状细胞缺失,大量炎性细胞浸润;关节囊滑膜表面粗糙,滑膜细胞增生、增厚,炎性细胞浸润明显;肠道菌群物种数目及均匀度减少,变形菌门、厚壁菌门、拟杆菌门相对丰度减少(P<0.05,P<0.01),脱硫杆菌门相对丰度增加(P<0.01),弯曲杆菌属、劳森氏菌属及假单胞菌属相对丰度增加(P<0.01),赫山单胞菌属、草螺菌属相对丰度降低(P<0.01);血清TNF-α、IL-1β、IL-6含量显著升高(P<0.01)。与模型组比较,益生菌组和电针组家兔膝关节周径显著减小、痛阈显著升高(P<0.01,P<0.05);肠黏膜损伤程度减轻,杯状细胞排列基本整齐,炎性细胞浸润减轻;滑膜细胞增生、增厚减轻,少量炎性细胞浸润;肠道菌群物种数目及均匀度增加,变形菌门、厚壁菌门、拟杆菌门相对丰度增加(P<0.05,P<0.01),脱硫杆菌门相对丰度减少(P<0.01),弯曲杆菌属、劳森氏菌属及假单胞菌属相对丰度减少(P<0.01),赫山单胞菌属、草螺菌属相对丰度增加(P<0.05,P<0.01);血清TNF-α、IL-1β、IL-6含量显著降低(P<0.01)。结论电针可显著改善RA家兔症状,降低关节滑膜炎症反应,其机制可能与调控肠道菌群结构有关。
Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund’s complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral“Zusanli”and“Dubi”for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1βand IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1βand IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1βand IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.
作者
刘翠
杜小正
井维尧
苏成红
刘莉梅
袁博
张星华
张枫帆
陈平
李向军
王海东
LIU Cui;DU Xiaozheng;JING Weiyao;SU Chenghong;LIU Limei;YUAN Bo;ZHANG Xinghua;ZHANG Fengfan;CHEN Ping;LI Xiangjun;WANG Haidong(Gansu University of Chinese Medicine,Lanzhou 730000,China;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Hospital of TCM,Lanzhou 730050,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2024年第4期124-131,共8页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家中医药管理局甘肃郑氏针法学术流派传承工作室(2305135901)
国家自然科学基金(82060891)
甘肃省自然科学基金(22JR11RA198、22JR11RA201)
甘肃省青年科技基金计划(20JR10RA344)
甘肃省针灸临床医学中心开放基金项目(ZJKF2203)
甘肃省皇甫谧针灸医院科研孵化项目(2020年)
甘肃中医药大学研究生创新创业基金项目(2023年)。
关键词
类风湿关节炎
电针
肠-关节轴
肠道菌群
炎性反应
兔
rheumatoid arthritis
electroacupuncture
gut-joint axis
intestinal flora
inflammatory reaction
rabbits
