白藜芦醇激活Nrf-2信号抑制H_(2)O_(2)诱导的骨关节炎软骨细胞凋亡、氧化损伤和炎症反应  

Resveratrol Activates Nrf-2 Signal to Inhibit Apoptosis,Oxidative Damage and Inflammatory Response of Osteoarthritis Chondrocyte Induced by H_(2)O_(2)

作　　者：杨波 龙慧 王郑钢[1] 曾德辉[1] 张彬[1] 龙秋平 YANG Bo;LONG Hui;WANG Zhenggang;ZENG Dehui;ZHANG Bin;LONG Qiuping(Department of Orthopedics,The Affiliated Nanhua Hospital of Nanhua University,Hengyang 421002,China;Department of Pain Rehabilitation,The Second Affiliated Hospital of Nanhua University,Hengyang 421001,China)

机构地区：[1]南华大学附属南华医院骨科,湖南衡阳421002 [2]南华大学附属第二医院疼痛康复科,湖南衡阳421001

出　　处：《中国现代应用药学》2021年第19期2359-2366,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：湖南省卫健委科研计划项目(C2019101);衡阳市科技局指导项目(S2018F9031022230)。

摘　　要：目的研究白藜芦醇在H_(2)O_(2)诱导骨关节炎软骨细胞凋亡、氧化损伤和炎症反应中的作用。方法通过MTT试验检测H_(2)O_(2)和(或)白藜芦醇处理原代软骨细胞增殖活性,流式细胞仪检测细胞凋亡情况;通过实时定量荧光PCR和Western blotting检测各处理组Nrf2-HO-1/NQO-1信号因子,抗氧化酶基因SOD-2、GPx4和CAT,炎症信号因子NF-κB、COX-2和iNOS的表达水平;流式细胞仪检测细胞ROS水平和脂质氧化水平;ELISA检测各处理组细胞炎症因子IL-6、IL-8、TNF-α的释放情况。结果白藜芦醇能够恢复H_(2)O_(2)诱导的原代软骨细胞凋亡,增加细胞增殖活性;上调Nrf2-HO-1/NQO-1信号因子和抗氧化酶基因SOD-2、GPx4和CAT的表达,降低H_(2)O_(2)诱导的ROS和脂质氧化水平;降低H_(2)O_(2)诱导的炎症信号因子NF-κB、COX-2和iNOS的表达水平,降低炎症因子IL-6、IL-8、TNF-α的释放。结论白藜芦醇可能通过增加转录因子Nrf-2的激活以及其直接抗氧化和抗炎作用来发挥对软骨细胞的保护作用,以改善骨关节炎的氧化损伤和炎症反应。OBJECTIVE To investigate the role of resveratrol on apoptosis,oxidative damage and inflammatory response of osteoarthritis chondrocytes induced by H_(2)O_(2).METHODS MTT assay was used to detect the proliferation of primary chondrocyte treated with H_(2)O_(2) and/or resveratrol,and flow cytometry was used to detect the apoptosis of chondrocyte.The expression levels of Nrf2-HO-1/NQO-1 signal factor,antioxidant enzyme gene SOD-2,GPx4 and CAT,inflammatory signal factor NF-κB,COX-2 and iNOS were detected by real-time quantitative fluorescence PCR and Western blotting.Flow cytometry was used to detect the level of ROS and lipid oxidation.The release of inflammatory cytokines IL-6,IL-8 and TNF-αin each treatment group was detected by ELISA.RESULTS Resveratrol could restore the apoptosis of primary chondrocyte induced by H_(2)O_(2) and increase the proliferation activity of chondrocyte;upregulate the expression of Nrf2-HO-1/NQO-1 signal factor and antioxidant gene SOD-2,GPx4 and CAT,and reduce the ROS and lipid oxidation level induced by H_(2)O_(2);reduce the expression of inflammatory signaling factors NF-κB,COX-2 and iNOS induced by H_(2)O_(2),and decrease the release of inflammatory factors IL-6,IL-8 and TNF-α.CONCLUSION Resveratrol may play a protective role on chondrocyte by increasing the activation of transcription factor Nrf-2 and its direct antioxidant and anti-inflammatory effects in order to improve the oxidative damage and inflammatory response of osteoarthritis.

关 键 词：白藜芦醇 骨关节炎 软骨细胞 H_(2)O_(2) Nrf-2 

分 类 号：R285.5[医药卫生—中药学]