白藜芦醇对AA大鼠关节成纤维样滑膜细胞凋亡诱导作用及可能机制  

Effect of resveratrol on apoptosis induction of fibroblast synovial cells and its possible mechanism

作　　者：宋先兵[1] 黄焱平 方安宁[1] 杨珺[1] 周文翰 王家昊 瞿子庭 朱浩辰 李娜[3] 陈晓宇[3] SONG Xian-bing;HUANG Yan-ping;FANG An-ning;YANG Jun;ZHOU Wen-han;WANG Jia-hao;QU Zi-ting;ZHU Hao-chen;LI Na;CHEN Xiao-yu(Dept of Human Anatomy,Anhui Medical College,Hefei 230061,China;Dept of Clinical Medicine,Anhui Medical University,Hefei 230032,China;Morphological Experiment Center,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医学高等专科学校人体解剖教研室,合肥230061 [2]安徽医科大学临床医学院,合肥230032 [3]安徽医科大学形态学实验中心,合肥230032

出　　处：《中国药理学通报》2020年第5期660-665,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金项目(No 81373421);安徽高校自然科学研究项目(No KJ2019ZD72);安徽省高校人才基金项目(No 1808085QH241,gxyq2019190);安徽医科大学基础与临床合作研究提升计划(No 2019xkjT027);大学生创新创业训练计划项目(No 201810366026,s201910366002);安徽医科大学“早期接触科研”项目(No 2019-ZQKY-16)。

摘　　要：目的探讨白藜芦醇(resveratrol,Res)对低浓度H2O2处理的大鼠佐剂性关节炎(adjuvant arthritis,AA)成纤维样滑膜细胞(FLS)影响,及与线粒体氧化应激蛋白去乙酰化酶3(sirtuins 3,SIRT3)、锰超氧化物歧化酶(MnSOD)的关系。方法20只SD大鼠,随机分为正常组、模型组,模型组足趾皮下注射弗氏完全佐剂,造模后d 28处死大鼠,检测大鼠血清氧化应激指标;免疫组织化学染色检测SIRT3、MnSOD在膝关节滑膜组织中的表达;CCK-8法观察不同浓度的H2O2,以及Res处理对FLS的增殖影响;Hoechst 33258和Western blot检测Res对低浓度H2O2处理FLS的凋亡和SIRT3、MnSOD蛋白表达的影响。结果与正常组大鼠比较,AA大鼠血清呈氧化应激状态,滑膜组织中SIRT3、MnSOD表达增加;低浓度H2O2可促进FLS增殖,Res能剂量依赖性抑制低浓度H2O2处理的增殖,增加FLS凋亡;且随着Res的剂量增加,FLS中SIRT3、MnSOD蛋白表达降低。结论低浓度H2O2可促进AA大鼠FLS生长,Res处理可抑制FLS增殖,促进FLS的凋亡,机制可能与Res抗氧化应激作用有关。Aim To explore the effect of resveratrol(Res)on fibroblast synovial cells(FLS)inadjuvant arthritis(AA)rats treated with low concentration of H2O2,and the role of mitochondrial oxidative stress proteins deacetylase 3(SIRT3)and manganese superoxide dismutase(MnSOD).Methods Twenty SD rats were randomly divided into normal group and model group.The AA model was induced by subcutaneous injection of the complete adjuvant in toes of model group.On 28th day after modeling,the rats were killed and the changes in serum oxidative stress index in two groups were detected.The expression of oxidative stress protein of SIRT3 and MnSOD in synovial tissues of knee joint of AA rats were detected by immunohistochemistry stainning.The effect of different concentrations of H2O2 or Res treatment on FLS proliferation was observed by CCK-8 method.The effect of Res on apoptosis and the expression proteins SIRT3 and MnSOD ofFLS treated with low H2O2 concentration were detected by Hoechst 33258 and Western blot.Results Compared with normal group,the serum of AA rats showed oxidative stress.The expression of SIRT3 and MnSOD increased in synovial tissues of AA model rats.Low concentration of H2O2 promoted FLS proliferation,and Res could dose-dependently inhibit proliferation treated with low concentration of H2O2,and increased FLS apoptosis.Moreover,with the increase of Res dose,the expression of SIRT3 and MnSOD protein decreased in FLS treated with low concentration H2O2.Conclusions AA rats are in a state of oxidative stress,low concentration of H2O2 can promote FLS growth in AA ras,and Res treatment can inhibit FLS proliferation,promoting FLS apoptosis.The mechanism may be related to the reduction of anti-oxidative stress effect.

关 键 词：成纤维样滑膜细胞 细胞增殖 细胞凋亡 线粒体 氧化应激 白藜芦醇 

分 类 号：R-332[医药卫生] R284.1