木瓜醇提物对大鼠类风湿性关节炎模型关节炎症及滑膜细胞凋亡的影响  

Effect of Chaenomelis Fructus Alcohol Extract on Arthritis Inflammation and Apoptosis of Synovial Cells in Rheumatoid Arthritis Model

作　　者：顾正位[1] 冯帅[1] 蒋海强[1] 魏盛[1] 梁晓东[1] 赵海军[1] 郭庆梅[1] GU Zheng-wei;FENG Shuai;JIANG Hai-qiang;WEI Sheng;LIANG Xiao-dong;ZHAO Hai-jun;GUO Qing-mei(Shandong University of Traditional Chinese Medicine,Ji'nan 250355,China)

机构地区：[1]山东中医药大学,济南250355

出　　处：《中国实验方剂学杂志》2020年第18期45-50,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)项目(2013CB531803);国家“重大新药创制”科技重大专项(2SQ2017ZX09301041);山东省重点研发计划项目(2018GSF119004);山东省高校青创人才引育计划项目(鲁教人字[2019]9号-201)。

摘　　要：目的:探讨木瓜醇提取物(CFE)对类风湿性关节炎(RA)大鼠模型的作用及机制。方法:将60只雄性SD大鼠随机分为正常组,模型组,CFE低、中、高剂量组及雷公藤多苷片组。除正常组外,其余各组分别从每只大鼠右后足跖皮内注入完全弗氏佐剂0.1 mL,复制RA模型。灌胃给药,CFE低、中、高剂量组剂量分别为0.15,0.30,0.60 g·kg-1·d-1,雷公藤多苷片组的剂量为0.009 g·kg-1·d-1,正常组及模型组灌胃等体积的蒸馏水,每天1次,连续30 d。观察大鼠足肿胀度、炎症指数、脏器指数,采用酶联免疫吸附测定(ELISA)检测血清中白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),白细胞介素-10(IL-10)及肿瘤坏死因子-α(TNF-α)的水平,苏木素-伊红(HE)染色观察各组大鼠滑膜组织病理变化情况,蛋白免疫印迹法(Western blot)检测大鼠关节B细胞淋巴瘤-2(Bcl-2),Bcl-2相关X蛋白(Bax)及死亡因子(Fas)蛋白表达情况。结果:与正常组比较,模型组大鼠足肿胀度、炎症指数显著升高(P<0.01);血清中的促炎因子IL-1β,IL-6,TNF-α水平显著升高(P<0.01),抗炎因子IL-10显著降低(P<0.01),滑膜组织中Bcl-2表达明显升高(P<0.05);与模型组比较,CFE中、高剂量组足趾肿胀程度及炎症指数显著降低(P<0.01),CFE各剂量组滑膜组织增生及炎症细胞浸润等病理变化减轻,血清中的促炎因子IL-1β,IL-6,TNF-α水平明显降低(P<0.05),抗炎因子IL-10明显升高(P<0.05),Bax,Fas的表达量升高,Bcl-2的蛋白表达量显著降低(P<0.01)。结论:CFE能够降低RA关节炎症程度,具有较好的抗RA功效,这可能与CFE诱导的关节滑膜细胞凋亡有关。Objective:To study the protective effect and mechanism of Chaenomelis Fructus alcohol extract(CFE)on the synovium of rheumatoid arthritis(RA).Method:Sixty male SD rats were randomly divided into normal group and model group.RA model was made by injection of complete Freund’s adjuvant,and then was randomly divided into model group,CFE low,medium and high dose group and Tripterygium glycoside group according to the inflammatory score.The CFE groups(0.15,0.30,0.60 g·kg-1·d-1)had intragastric administration once a day for 30 d after the model establishment.The blank control group and the model group were given the same volume saline water by gavage.After all the drugs were given,the blood,joint tissues and synovium tissue of rats were collected.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10)and tumor necrosis factor(TNF)-αin serum were detected by enzyme linked immunosorbent assay(ELISA),the pathological changes of synovium were observed by hematoxylin eosin(HE)staining,and the expressions of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and death factor(Fas)in joints were detected by Western blot.Result:Compared with normal group,the swelling degree and inflammation index of rats’feet in model group increased significantly,the levels of inflammatory factors IL-1β,IL-6,TNF-αin serum increased(P<0.01),anti-inflammatory factor IL-10 decreased(P<0.01),the protein expression of Bax,Fas and Bcl-2 increased,and the statistical results of Bcl-2 showed significant difference(P<0.05).Compared with model group,the swelling degree and inflammatory index of the plantar of RA rats were improved in the middle and high dose groups of CFE(P<0.01),the pathological changes such as synovial tissue hyperplasia and inflammatory cell infiltration were reduced in each dose group,and the levels of IL-1β,IL-6 and TNF-αin serum were reduced(P<0.05),anti inflammatory factor IL-10 increased(P<0.05),the disorder of inflammatory cytokine in the model was corrected,Bax,Fas expression increased,B

关 键 词：类风湿性关节炎 木瓜醇提物 凋亡 炎症 佐剂型关节炎 

分 类 号：R2-0[医药卫生—中医学] R289