莱菔硫烷干预晚期糖基化终末产物诱导血管平滑肌细胞转分化研究  

Intervention of Sulforaphane on Advanced Glycation End Products-Induced Transdifferentiation of Vascular Smooth Muscle Cells

作　　者：李进冬 徐震[1] 张楠 高一 瞿建江 季晓慧 LI Jindong;XU Zhen;ZHANG Nan;GAO Yi;QU Jianjiang;JI Xiaohui(The Affiliated Taizhou People's Hospital of Nanjing Medical University,Taizhou,Jiangsu,China 225300;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou,Jiangsu,China 221004;Wuxi People's Hospital Affiliated to Nanjing Medical University,Wuxi,Jiangsu,China 214023)

机构地区：[1]南京医科大学附属泰州人民医院,江苏泰州225300 [2]江苏省新药研究与临床药学重点实验室,江苏徐州221004 [3]南京医科大学附属无锡人民医院,江苏无锡214023

出　　处：《中国药业》2023年第24期68-71,共4页China Pharmaceuticals

基　　金：江苏省新药研究与临床药学重点实验室开放课题[KFKT-2108];江苏省泰州市“凤城英才计划”青年科技人才托举工程项目[202210];江苏省泰州市人民医院院级科研项目[ZL202025]。

摘　　要：目的探讨莱菔硫烷(SFN)抑制晚期糖基化终末产物(AGE)诱导的大鼠血管平滑肌细胞(VSMC)向成骨细胞转分化的作用及机制。方法取细胞培养传代至第5代的VSMC,分为对照组[普通培养基培养2 d+含牛血清白蛋白(BSA)的培养基培养5 d]、AGE组(普通培养基培养2 d+含200 mg/L的AGE培养基培养5 d)、SFN组(含10μmol/L的SFN培养基培养2 d+含BSA的培养基培养5 d)及SFN+AGE组(含10μmol/L的SFN培养基培养2 d+含200 mg/L的AGE培养基培养5 d)。检测各组VSMC钙离子、丙二醛(MDA)及超氧化物歧化酶(SOD)水平;采用Western blot法检测细胞内α-平滑肌肌动蛋白(α-SMA)、Runt相关转录因子2(RUNX2)、骨桥蛋白(OPN)、核因子E2相关因子2(Nrf2)、醌氧化还原酶1(NQO1)及血红素加氧酶-1(HO-1)蛋白的表达水平。结果与AGE组比较,SFN+AGE组细胞内钙离子、MDA水平均显著降低,SOD水平显著升高(P<0.05);OPN和RUNX2蛋白表达水平均显著降低,α-SMA蛋白表达水平显著升高(P<0.05);Nrf2,NQO1,HO-1蛋白表达水平均显著升高(P<0.05)。结论SFN可提高细胞抗氧化应激能力,从而抑制AGE诱导的VSMC向成骨细胞转分化,其机制可能与细胞内Nrf2信号通路的激活有关。Objective To investigate the inhibitory effect and mechanism of sulforaphane(SFN)on the advanced glycation end products(AGEs)-induced transdifferentiation of rat vascular smooth muscle cells(VSMCs)into osteoblasts.Methods After subculture,the fifth generation of VSMCs were selected and divided into the control group[cultured in ordinary medium for 2 d and medium containing bovine serum albumin(BSA)for 5 d],the AGE group(cultured in ordinary medium for 2 d and medium containing 200 mg/L of AGE for 5 d),the SFN group(cultured in medium containing 10μmol/L of SFN for 2 d and medium containing BSA for 5 d),and the SFN+AGE group(cultured in medium containing 10μmol/L of SFN for 2 d and medium containing 200 mg/L of AGE for 5 d).VSMCs in each group were collected to detect the calcium ion,malondialdehyde(MDA)and superoxide dismutase(SOD)levels and the expression levels ofα-smooth muscle actin(α-SMA),Runt-related transcription factor 2(RUNX2),osteopontin(OPN),nuclear factor erythroid 2-related factor 2(Nrf2),NADPH quinone oxidoreductase 1(NQO1)and heme oxygenase-1(HO-1)proteins by the western blot.Results Compared with those in the AGE group,the calcium ion and MDA levels in the SFN+AGE group were significantly lower,the SOD level was significantly higher(P<0.05);the expression levels of OPN and RUNX2 proteins were significantly lower,the expression level ofα-SMA protein was significantly higher(P<0.05);the expression levels of Nrf2,NQO1 and HO-1 proteins were significantly higher(P<0.05).Conclusion SFN can improve the anti-oxidative stress ability of cells,thereby inhibiting AGE-induced transdifferentiation of VSMCs into osteoblasts,its mechanism may be related to the activation of the intracellular Nrf2 signaling pathway.

关 键 词：莱菔硫烷 晚期糖基化终末产物 血管平滑肌细胞 转分化 氧化应激 核因子E2相关因子2信号通路 

分 类 号：R965[医药卫生—药理学]