Sheng Rui, Gu Zhen-lun, Xie Mei-lin, Zhou Wen-xuan, Guo Ci-yi
Department of Pharmacology, Medical School of Soochow University, Suzhou 215123, China.
Acta Pharmacol Sin. 2007 Feb;28(2):191-201. doi: 10.1111/j.1745-7254.2007.00495.x.
To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis.
Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2.
In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6 weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. In the Western blot analysis, EGCG significantly inhibited pressure overload-induced p53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry.
EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload induced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.
研究表没食子儿茶素没食子酸酯(EGCG)对压力超负荷及过氧化氢(H2O2)诱导的心肌细胞凋亡的影响。
通过腹主动脉缩窄建立大鼠心肌肥厚模型。分别以25、50和100mg/kg的剂量对大鼠进行EGCG灌胃给药。将培养的新生大鼠心肌细胞用EGCG进行预孵育,并用H2O2诱导氧化应激损伤。
在大鼠腹主动脉缩窄诱导的心肌肥厚模型中,与模型组相比,EGCG 25、50和100mg/kg灌胃6周,可剂量依赖性降低收缩压(SBP)和心脏重量指数,降低血清和心肌中丙二醛(MDA)含量,提高超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性。此外,50和100mg/kg的EGCG治疗显著改善心脏结构,在苏木精-伊红(HE)和维多利亚蓝(VG)染色中抑制纤维化,并通过末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记(TUNEL)法检测发现肥厚心肌中的凋亡心肌细胞减少。在蛋白质印迹分析中,EGCG显著抑制压力超负荷诱导的p53增加和bcl-2减少。在H2O2诱导的心肌细胞损伤中,当与心肌细胞预孵育6-48小时时,12.5-200mg/L的EGCG通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法检测可提高细胞活力。EGCG还可减轻H2O2诱导的乳酸脱氢酶(LDH)释放和MDA形成。同时,50和100mg/L的EGCG在流式细胞术中显著抑制心肌细胞凋亡率。
EGCG可抑制压力超负荷诱导的心肌肥厚中的心肌细胞凋亡和氧化应激。此外,EGCG在体外可防止氧化应激诱导的心肌细胞凋亡。其机制可能与EGCG对p53诱导和bcl-2减少的抑制作用有关。