Muhammed Ibrahim, Sankar Suruthi, Govindaraj Sakthivel
Physiology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
J Cardiovasc Pharmacol. 2018 Feb;71(2):65-75. doi: 10.1097/FJC.0000000000000545.
The objective of the present study is to evaluate the effect of epigallocatechin gallate (EGCG) on aging-mediated cardiac hypertrophy, fibrosis, and apoptosis. The Wistar albino rats were divided into 4 groups (n = 18). Group I: young (3 months), group II: aged (24-26 months), group III: aged + EGCG (200 mg/kg for 30 days), and group IV: young + EGCG. At the end of 30 days, EGCG administration to the aged animals showed significant (P < 0.001) reduction of low-density lipoprotein, very low-density lipoprotein, triglyceride, total cholesterol with concomitant increase of high-density lipoprotein (P < 0.001) when compared with aged rats. Increased (P < 0.001) heart volume, weight with concomitant increase of left ventricular wall thickness, and reduced ventricular cavity were observed in aged rats supplemented with EGCG compared with aged animals. Histology and histomorphometry study of aged animals treated with EGCG showed marked increases in the diameter and volume of cardiomyocytes with concomitant reduction of numerical density when compared with aged animals. Reduced reactive oxygen species (P < 0.001) production with association of increased antioxidant defense system (P < 0.001) in aged hearts supplemented with EGCG when compared with aged animals. TUNEL staining and fibrosis showed a marked increase in apoptotic cell death (P < 0.001) and collagen deposition (P < 0.001) in aged animals treated with EGCG when compared with aged animals. Aged animals treated with EGCG showed a marked increase in protein expression of TGFβ, TNFα, and nuclear factor kappa B (NF-κB) and significant (P < 0.001) alteration in the gene expression of TGFβ, TNFα, NF-κB, α-SMA, and Nrf2 when compared with aged animals. Taken together, it is evident that EGCG may potentially inhibit aging-induced cardiac hypertrophy, fibrosis, and apoptosis, thereby preserving cardiac function. The proposed mechanism would be inhibition of reactive oxygen species-dependent activation of TGFβ1, TNFα, and NF-κB signaling pathway. Hence, the present study suggests that EGCG can be useful to fight against aging-induced cardiac hypertrophy, fibrosis, and apoptosis.
本研究的目的是评估表没食子儿茶素没食子酸酯（EGCG）对衰老介导的心脏肥大、纤维化和细胞凋亡的影响。将Wistar白化大鼠分为4组（n = 18）。第一组：年轻（3个月），第二组：老年（24 - 26个月），第三组：老年 + EGCG（200 mg/kg，持续30天），第四组：年轻 + EGCG。在30天结束时，与老年大鼠相比，给老年动物施用EGCG后，低密度脂蛋白、极低密度脂蛋白、甘油三酯、总胆固醇显著降低（P < 0.001），同时高密度脂蛋白增加（P < 0.001）。与老年动物相比，补充EGCG的老年大鼠心脏体积和重量增加（P < 0.001），同时左心室壁厚度增加，心室腔减小。与老年动物相比，对用EGCG处理的老年动物进行组织学和组织形态计量学研究显示，心肌细胞直径和体积显著增加，同时数量密度降低。与老年动物相比，补充EGCG的老年心脏中活性氧产生减少（P < 0.001），同时抗氧化防御系统增强（P < 0.001）。TUNEL染色和纤维化显示，与老年动物相比，用EGCG处理的老年动物凋亡细胞死亡（P < 0.001）和胶原沉积显著增加（P < 0.001）。与老年动物相比，用EGCG处理的老年动物TGFβ、TNFα和核因子κB（NF - κB）的蛋白表达显著增加，TGFβ、TNFα、NF - κB、α - SMA和Nrf2的基因表达发生显著改变（P < 0.001）。综上所述，显然EGCG可能潜在地抑制衰老诱导的心脏肥大、纤维化和细胞凋亡，从而保护心脏功能。推测的机制是抑制依赖活性氧的TGFβ1、TNFα和NF - κB信号通路的激活。因此，本研究表明EGCG可用于对抗衰老诱导的心脏肥大、纤维化和细胞凋亡。
