EGCG Inhibits Proliferation of Cardiac Fibroblasts in Rats with Cardiac Hypertrophy
EGCG Inhibits Proliferation of Cardiac Fibroblasts in Rats with Cardiac Hypertrophy
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EGCG 抑制心脏肥大大鼠心脏成纤维细胞的增殖
DOI：
10.1055/s-0028-1088387
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发表时间：
2009-02-01
期刊：
影响因子：
2.7
通讯作者：
Guo, Ci-yi
中科院分区：
文献类型：
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作者：
Sheng, Rui;Gu, Zhen-lun;Guo, Ci-yi
本研究旨在探讨表没食子儿茶素没食子酸酯(EGCG)对心肌肥厚时心肌纤维化和细胞增殖的影响。采用腹主动脉缩窄法建立大鼠心肌肥厚模型，给予EGCG 25、50、100 mg/kg灌胃，连续6周。结果表明，在心肌肥厚大鼠，EGCG(25-100 mg/kg)可明显降低心脏重量指数，降低血浆心钠素和内皮素水平，升高血清和心肌组织中NO的氧化产物亚硝酸盐水平。EGCG还可降低肥厚心肌羟脯氨酸浓度，减少增殖细胞核抗原表达。Western印迹分析显示，EGCG能显著抑制压力超负荷引起的c-myc升高。在培养的新生大鼠心脏成纤维细胞中，EGCG12.5-200 mg/L作用6-48h可抑制血清诱导的细胞增殖。与Ang II组比较，EGCG12.5~100 mg/L剂量依赖性地抑制血管紧张素II(Ang II)诱导的成纤维细胞增殖和DNA合成，显著增加培养上清液中亚硝酸盐水平，上调诱导型一氧化氮合酶蛋白表达。N-奥米伽-硝基-L-精氨酸甲酯盐酸盐可部分阻断EGCG对血管紧张素Ⅱ诱导的细胞增殖的抑制作用。这些结果表明，EGCG在体内和体外都能抑制心脏成纤维细胞的增殖，从而防止心肌肥厚时的心肌纤维化。EGCG可能通过诱导NO的产生发挥其心脏保护作用。
This Study was carried out in order to investigate the effects of epigallocatechin gallate (EGCG) on myocardial fibrosis and cell proliferation in cardiac hypertrophy. Cardiac hypertrophy was established in rats by abdominal aortic constriction, and EGCG at doses of 25, 50 and 100 mg/kg was administered intragastrically for 6 weeks. The results showed that in the rats with cardiac hypertrophy, EGCG at 25-100 mg/kg close-dependently reduced heart weight indices, decreased atrial natriuretic polypeptide and endothelin levels in plasma, but increased nitrite (the oxidative product of NO) levels in the serum and in the myocardium. EGCG also reduced the hydroxyproline concentration and decreased the proliferating cell nuclear antigen expression in the hypertrophic myocardium. EGCG remarkably inhibited pressure overload-induced c-myc increase in Western blot analysis. In Cultured newborn rat cardiac fibroblasts, treatment with EGCG at 12.5-200 mg/L for 6-48 h decreased cell proliferation induced by serum. EGCG at 12.5-100 mg/L dose-dependently inhibited cell proliferation and DNA synthesis of fibroblasts induced by angiotensin II (Ang II) at 1 mu mol/L. EGCG also significantly increased nitrite levels in culture medium, and up-regulated inducible nitric oxide synthase protein expression if compared with the Ang II group. The inhibitory effect of EGCG on cell proliferation induced by Ang II was partly blocked by pretreatment with N-omega-nitro-L-arginine methyl ester hydrochloride. These results suggest that EGCG inhibits the proliferation of cardiac fibroblasts both in vivo and in vitro, thereby preventing myocardial fibrosis in cardiac hypertrophy. EGCG might exert its cardiac protective action through induction of NO production.