基于雌激素受体探讨梓醇对抗糖剥夺心肌细胞损伤的作用  

Effect of catalpol on “glucose deprivation” cardiomyocyte injury based on estrogen receptor

作　　者：王素云[1,2] 卢颖 蔡丹凤[1,2] 童静 成鹏 余夕潮 李育 卞慧敏 WANG Su-yun;LU Ying;CAI Dan-feng;TONG Jing;CHENG Peng;YU Xi-chao;LI Yu;BIAN Hui-min(School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China;School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China;School of Pharmacy,School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]南京中医药大学江苏省中药药效与安全性评价重点实验室,江苏南京210023 [3]南京中医药大学医学与生命科学学院,江苏南京210023

出　　处：《中国药理学通报》2019年第6期786-792,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173190;81774029);江苏省中药药效与安全性评价重点实验室资助项目(No JKLPSE201605;JKLPSE201809);江苏省高校中药学优势学科建设工程资助项目(PAPD);江苏省研究生科研与实践创新计划(KYCX18-1635;KYCX18-1594)

摘　　要：目的基于雌激素受体,探讨梓醇介导自噬对糖剥夺心肌细胞氧化损伤的作用和机制。方法采用糖剥夺6 h复制大鼠心肌细胞(H9c2)损伤模型,观察中药地黄中有效成分梓醇对其保护作用及机制。将细胞分为5组:对照组、模型组、梓醇(0. 28、2. 8、28μmol·L^(-1))组。检测梓醇对细胞中活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)的影响;电镜观察梓醇对细胞自噬的影响。利用雌激素受体(ER)阻断剂,探究梓醇对抗氧化损伤机制是否由ER介导。进一步采用慢病毒转染使ERα低表达后,观察梓醇作用前后氧化损伤、自噬水平的变化。结果与空白对照组相比,模型组ROS、MDA水平升高,SOD水平降低,自噬相关蛋白表达无明显差异;与模型组比较,梓醇能够升高SOD水平降低氧化损伤,升高自噬水平。采用慢病毒转染ERα后,与空载病毒梓醇组相比,梓醇抑制氧化损伤、促进自噬的作用被逆转。结论梓醇能通过上调ERα表达激活自噬,发挥抗氧化损伤、保护心肌的作用。Aim To investigate the effect of catalpol-mediated autophagy on oxidative damage of cardiomyocytes induced by glucose deprivation based on estrogen receptor(ER) and the related mechanism. Methods The cardiomyocytes (H9c2) injury model in rat was induced by glucose deprivation for 6 h. The protective effect of catalpol on H9c2 injury and its mechanism were observed. The cells were divided into five groups: control group, model group, catalpol group (0.28, 2.8, 28 μmol·L -1 ). The effects of catalpol on reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) in cells were detected, and the effect of catalpol on autophagy was assessed by electron microscopy. ER blockers was used to detect whether the protective effect of catalpol on oxidative damage was related to ER. Lentivirus transfection was used to lower the expression of ER alpha, and the oxidative damage and autophagy of H9c2 treated with catapol or not were observed. Results Compared with control group, the levels of ROS and MDA increased and SOD decreased in model group, and there was no significant difference in the expression of autophagy related proteins. Compared with model group, catalpol could reduce oxidative damage and increase autophagy level. After transfection of ER alpha with lentivirus, catalpol inhibited the level of oxidative damage and promoted the effect of autophagy compared with the empty virus catalpol group. Conclusions Catalpol can activate autophagy by up-regulating the expression of ER alpha and inhibiting the oxidative damage of cardiomyocytes.

关 键 词：梓醇 自噬 大鼠心肌细胞 氧化损伤 活性氧 糖剥夺 

分 类 号：R-332[医药卫生] R284.1