电针调控HIF-1α/VEGF信号通路对类风湿性关节炎模型踝关节病理学改变的影响  

Electroacupuncture influences pathological changes of the ankle in rats with rheumatoid arthritis by regulating the HIF-1α/VEGF signaling pathway

作　　者：张勇[1] 李春花[1] 熊冻 梁艳[1] ZHANG Yong;LI Chunhua;XIONG Dong(People’s Hospital Affiliated to Chongqing Three Gorges Medical College,Chongqing 404100,China)

机构地区：[1]重庆三峡医药高等专科学校附属人民医院,重庆市404100

出　　处：《河北医药》2024年第21期3227-3231,共5页Hebei Medical Journal

基　　金：重庆市基础与前沿研究计划项目(编号:Y2020023243)。

摘　　要：目的探讨电针通过调控HIF-1α/VEGF信号通路活性对类风湿性关节炎(RA)大鼠踝关节病理损伤的影响。方法选取50只SD大鼠,随机分为Sham组(空白对照)、RA组(大鼠构建RA模型)、电针组(RA组大鼠给予电针治疗)、CAY10585组(RA大鼠腹腔内注射HIF-1α/VEGF信号通路抑制剂)、电针+CAY10585组(电针组大鼠腹腔注射HIF-1α/VEGF信号通路抑制剂),每组10只。模型建立后观察各组大鼠基本形态;8周后处死大鼠,比较治疗后大鼠踝关节直径;取大鼠踝关节行HE染色,观察整体病理形态及踝关节病理特征(滑膜细胞增殖、细胞侵蚀、血管翳形成、炎性细胞浸润、骨侵蚀)病理评分;酶联免疫吸附法(ELISA)检测5组大鼠血清炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平;Western-blot检测大鼠踝关节组织内软骨基质因子Ⅱ型胶原(CollagenⅡ)、C端肽(CTXⅡ)、Ⅱ型胶原C前肽(CPⅡ)蛋白表达。结果与Sham组比较,RA模型建立可以上调大鼠踝关节直径,踝关节滑膜细胞增殖、细胞侵蚀、血管翳形成、炎性细胞浸润、骨侵蚀病理评分,血清炎性因子(TNF-α、IL-6)水平均明显提升(P<0.05),关节滑膜上皮复层出现增生、间质水肿以及炎性细胞浸润的现象;电针干预可以下调大鼠踝关节直径、踝关节滑膜细胞增殖、细胞侵蚀、血管翳形成、炎性细胞浸润、骨侵蚀病理评分,血清炎性因子(TNF-α、IL-6)水平(P<0.05),同时踝关节病理形态明显得到缓解;CAY10585干预再次增加RA大鼠病理形态,破骨细胞明显增加,骨质出现侵蚀、溶解骨层及炎性细胞浸润的现象,踝关节直径、踝关节滑膜细胞增殖、细胞侵蚀、血管翳形成、炎性细胞浸润、骨侵蚀病理评分,血清炎性因子(TNF-α、IL-6)水平再次提升(P<0.05);电针干预可以逆转CAY10585组大鼠趋势,再次下调大鼠踝关节直径、踝关节滑膜细胞增殖、细胞侵蚀、血管翳形成、炎性细胞浸润、骨侵蚀病�Objective To explore the effect of electroacupuncture on pathological changes of the ankle in rats with rheumatoid arthritis(RA)by regulating the hypoxia inducible factor 1 alpha(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods A total of 50 Sprague-Dawley(SD)rats were randomly assigned into Sham group(blank control),RA group(RA modeling),electroacupuncture group(RA modeling and intervention of electroacupuncture),and CAY10585 group(RA modeling and intraperitoneal injection of the HIF-1α/VEGF signaling pathway inhibitor),electroacupuncture+CAY10585 group(RA modeling plus electroacupuncture and intraperitoneal injection of the HIF-1α/VEGF signaling pathway inhibitor),with ten rats per group.After establishing the model,the basic morphology of rats in each group was observed.Rats were sacrificed after 8 weeks.The diameter of rat ankle after treatment was measured.The hematoxylin and eosin(H&E)staining of the rat ankle was performed to observe the overall pathological morphology and grade pathological characteristics of synovial cell proliferation,cell erosion,pannus formation,inflammatory cell infiltration and bone erosion.Enzyme-linked immunosorbent assay(ELISA)was performed to measure serum inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Western blot was performed to detect the protein expressions of cartilage matrix factor typeⅡcollagen(CollagenⅡ),C-terminal peptide(CTXⅡ),and typeⅡcollagen C-precursor peptide(CPⅡ)in rat ankle joint tissues.Results Compared with those of the Sham group,rats in the RA group had significantly higher diameter of the ankle,pathological scores of proliferation of synovial cells in the ankle joint,cell erosion,pannus formation,inflammatory cell infiltration and bone erosion,and serum TNF-αand IL-6 levels(P<0.05),as well as the presences of hyperplasia,interstitial edema,and inflammatory cell infiltration in the synovial epithelial layer of the ankle.The intervention of electroacupuncture significantly reduced the diame

关 键 词：类风湿性关节炎 电针 踝关节损伤 膝关节疼痛 HIF-1α/VEGF信号通路 

分 类 号：R593.22[医药卫生—内科学]