鼠尾草酚调控Nrf2/HO-1信号通路介导成骨分化治疗骨质疏松症的研究  

Study on the regulation of Nrf2/HO-1 signaling pathway mediated by carnosol in the treatment of osteoporosis

作　　者：易艳梓 来孟琪 陈秀天 江禹来 张阔 郑泽炜 张庆文 YI Yanzi;LAI Mengqi;CHEN Xiutian;JIANG Yulai;ZHANG Kuo;ZHENG Zewei;ZHANG Qingwen(Third Clinical Medical College of Guangzhou University of Chinese Medicine,Guangdong Province,Guangzhou510112,China;Joint Center,Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong Province,Guangzhou510106,China)

机构地区：[1]广州中医药大学第三临床医学院,广东广州510112 [2]广州中医药大学第三附属医院关节中心,广东广州510106

出　　处：《中国医药导报》2024年第22期40-45,50,共7页China Medical Herald

基　　金：广东省中医药局中医药科研项目立项项目(20223012)。

摘　　要：目的研究鼠尾草酚对MC3T3-E1细胞氧化应激损伤状态下成骨分化的影响及其作用机制,阐述鼠尾草酚治疗骨质疏松症的潜力。方法MC3T3-E1细胞加入不同浓度(0.0、1.0、2.5、5.0、10.0、25.0、50.0、100.0μmol/L)的鼠尾草酚干预24 h,分析对成骨细胞增殖的影响,选择最佳的鼠尾草酚干预浓度进行后续实验。将细胞分为对照组(不做任何处理)、模型组(250.0μmol/L H_(2)O_(2)干预)、鼠尾草酚低浓度组(250.0μmol/L H_(2)O_(2)+2.5μmol/L鼠尾草酚)、鼠尾草酚高浓度组(250.0μmol/L H_(2)O_(2)+5.0μmol/L鼠尾草酚),各组细胞干预24 h。比较各组活性氧(ROS)、丙二醛(MDA),碱性磷酸酶(ALP)活性,矿化面积比例,Runx2、Osterix、COL1A mRNA表达及Nrf2、HO-1、SOD2 mRNA和蛋白表达。结果选择2.5、5.0μmol/L鼠尾草酚进行后续实验。与对照组比较,模型组ROS、MDA含量及Nrf2、HO-1 mRNA和蛋白表达升高;ALP活性,矿化面积比例,Runx2、Osterix、COL1A mRNA及SOD2 mRNA和蛋白表达降低(P<0.01)。与模型组比较,鼠尾草酚低、高浓度组ROS、MDA含量降低;ALP活性,矿化面积比例,Runx2、Osterix、COL1A mRNA表达及Nrf2、HO-1、SOD2 mRNA和蛋白表达升高(P<0.01)。与鼠尾草酚低浓度组比较,鼠尾草酚高浓度组ALP活性、矿化面积比例及HO-1蛋白表达升高(P<0.05);鼠尾草酚低、高浓度组ROS,MDA含量,Runx2、Osterix、COL1A、HO-1 mRNA及Nrf2、SOD2 mRNA和蛋白表达比较,差异无统计学意义(P>0.05)。结论鼠尾草酚可通过激活Nrf2/HO-1信号通路调控MC3T3-E1细胞的氧化应激状态,进而促进成骨分化,减轻骨质疏松进程中骨代谢失衡。Objective To study the effect of carnosol on osteogenic differentiation of MC3T3-E1 cells under oxidative stress and its mechanism, and to expound the potential of carnosol in the treatment of osteoporosis. Methods MC3T3-E1 cells were treated with different concentrations of carnosol (0.0, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 μmol/L) for 24 h, the effects on osteoblast proliferation were analyzed, and the optimal concentration of carnosol was selected for follow-up experiments. The cells were divided into control group (no treatment), model group (250.0 μmol/L H_(2)O_(2) intervention), carnosol low concentration group (250.0 μmol/L H_(2)O_(2)+2.5 μmol/L carnosol) and carnosol high concentration group (250.0 μmol/L H_(2)O_(2)+5.0 μmol/L carnosol), each group was treated for 24 h. Reactive oxygen species (ROS), malondialdehyde(MDA), alkaline phosphatase (ALP) activity, mineralized area ratio, Runx2, Osterix, and COL1A mRNA expressions, and Nrf2, HO-1, and SOD2 mRNA and protein expressions were compared among all groups. Results The concentration of 2.5 μmol/L and 5.0 μmol/L carnosol were selected for follow-up experiments. Compared with control group, ROS and MDA contents, Nrf2 and HO-1 mRNA and protein expressions were increased;ALP activity, mineralized area ratio, Runx2, Osterix, COL1A mRNA expressions, and SOD2 mRNA and protein expressions were decreased in model group (P<0.01). Compared with model group, ROS and MDA contents were decreased;ALP activity, mineralized area ratio, Runx2, Osterix and COL1A mRNA expressions, and Nrf2, HO-1 and SOD2 mRNA and protein expressions were increased in low and high concentration groups (P<0.01). Compared with carnosol low concentration group, ALP activity, mineralized area ratio, and HO-1 protein expression were increased in carnosol high concentration group (P<0.05);there were no significant differences in ROS, MDA contents, Runx2, Osterix, COL1A, HO-1 mRNA expressions, and Nrf2, SOD2 mRNA and protein expressions between carnosol low and high concentration gr

关 键 词：鼠尾草酚 骨质疏松症 成骨分化 Nrf2/HO-1信号通路 

分 类 号：R965[医药卫生—药理学]