摘要
目的研究在H9C2细胞中姜黄素衍生物H79L43H3对高糖诱导H9C2心肌细胞肥大和纤维化的保护作用以及对ERK、NRF2信号通路的调节作用。方法将心肌细胞分为5组,即对照组、模型组、干预组(2.5、5、10μmol/L)。以不同浓度姜黄素衍生物H79L43H3干预1h后,模型组和干预组予以高糖(33mmol/L)干预。高糖干预24h后,用ELISA方法检测细胞培养液炎性因子IL-6、TNF-α分泌量的变化:用荧光定量PCR和Western blot法检测Collegan-Ⅰ、TGF-β、ANP、MAPK和NRF2通路m RNA及蛋白表达;罗丹明鬼笔环肽染色显示肌动蛋白肌丝的结构。DHE染色显示活性氧簇(ROS)的含量。结果与对照组相比,模型组Collegan-Ⅰ、TGF-β水平明显升高(P<0.05),H79L43H3干预组具有剂量依赖性的抑制作用(P<0.05)。与对照组相比,模型组ERK通路明显激活,NRF2通路被抑制,H79L43H3干预组可逆转这一改变(P<0.05)。结论姜黄素衍生物H79L43H3可明显抑制H9C2细胞中高糖诱导的心肌肥大和纤维化改变,可能与其抑制炎性因子释放及抗氧化作用有关,提示H79L43H3可能有望成为防治糖尿病心肌病的新药。
Objective To explore the protection of curcumin derivatives H79L43H3 on high glocose-induced myocyte hypertrophy and fibrosis in H9C2 cells and analyze possible role of H79L43H3 on regulating ERK and NRF2 signaling. Methods Myocardial cells were divided into 5 groups：control group, model group and treatment group （2.5, 5, 10μmol/L）.After incubated with different concentrations of curcumin derivatives H79L43H3 for 1h, the model group and treatment groups were exposed to high glucose （33mmol/L）. ELISA method was used for detecting changes of IL-6 and TNF-α production in culture solution.By fluorescence quantitative PCR and western blotting, Collegan-Ⅰ, TGF-β, ANP, MAPK and NRF pathways were tested. Rhodamine phalloidin showed actin microfilament. dhe staining were used to detect oxidation level. Results Compared with control group, the levels of Collegan-Ⅰ, TGF-β was significantly increased in model group（P〈0.05）. Meanwhile it was significantly reduced in a dose-dependent manner in the treatment group（P〈0.05）. Compared with the control group, the ERK pathway was significantly activated and the NRF pathway was inhibited in the model group. And it was reversed in the treatment group（P〈0.05）. Conclusion Curcumin derivative H79L43H3 can obviously inhibit myocardial hypertrophy and fibrosis in H9C2 cells, which may be related to the inhibition of inflammatory factor release and antioxidant activity. H79L43H3 might be expected to become a new drug for the prevention and control of diabetic cardiomyopathy.
作者
洪莹
郑超
Hong Ying;Zheng Chao(The Second School of Medicine,Wenzhou Medical University The Second Affiliated Hospital,Zhejiang 325027,China)
出处
《医学研究杂志》
2018年第8期18-23,共6页
Journal of Medical Research
基金
国家自然科学基金资助项目(81670777)
关键词
糖尿病心肌病
姜黄素衍生物
炎症
氧化应激
Diabetic eardiomyopathy
Cureumin derivatives
Inflammation
Oxidative stress
