Role of 5-HT2B receptors in cardiomyocyte apoptosis in noradrenaline-induced cardiomyopathy in rats
Role of 5-HT2B receptors in cardiomyocyte apoptosis in noradrenaline-induced cardiomyopathy in rats
复制标题
5-HT2B受体在去甲肾上腺素心肌病大鼠心肌细胞凋亡中的作用
DOI：
10.1111/j.1440-1681.2010.05388.x
复制
发表时间：
2010-07-01
影响因子：
2.9
通讯作者：
Zhao, Ming-Gao
中科院分区：
文献类型：
--
作者：
Bai, Chong-Feng;Liu, Jin-Cheng;Zhao, Ming-Gao
P > 1。5-羟色胺（5-羟色胺；5-HT）通过激活5-HT受体在心脏肥厚的发生中起重要作用。本研究的目的是探讨5-HT2B受体在心肌细胞凋亡和心肌肥大与去甲肾上腺素（NA）超载相关的发展中的作用。大鼠腹腔注射1.5 mg/kg NA，连续4周诱导心肌肥厚。从第15天开始，每天注射2次5-HT2B受体拮抗剂SB 204741 （i.p， 0.5或2 mg/kg）或SDZ SER 082 (i.p, 1 mg/kg)，连续14天。全细胞膜片钳技术用于记录新分离的心室心肌细胞的离子电流。采用Western blot和末端脱氧核糖核苷酸转移酶介导的dutp -地高辛缺口末端标记法（TUNEL）评估心肌凋亡。体内NE超载诱导的肥厚左心室中5-HT2B受体表达增强。5-HT2B受体拮抗剂SB 204741可部分逆转NE过载引起的心肌肥厚（P < 0.05），降低心室心肌细胞l型钙电流（P < 0.05）。此外，SB 204741显著降低心肌细胞凋亡，表达Bax和caspase 3下调（P < 0.05），表达抗凋亡Bcl-2蛋白上调（P < 0.05）。总之，这些数据表明，在肾上腺素能刺激增加时，5-HT2B受体参与了与心脏重构相关的凋亡事件的产生。
P>1. Serotonin (5-hydroxytryptamine; 5-HT) plays important roles in the development of cardiac hypertrophy via activation of 5-HT receptors. The aim of the present study was to investigate the role of 5-HT2B receptors in the development of cardiomyocyte apoptosis and hypertrophy associated with noradrenaline (NA) overload.2. Cardiac hypertrophy was induced in rats by intraperitoneal injection of 1.5 mg/kg NA for 4 weeks. Starting from Day 15, 5-HT2B receptor antagonist SB 204741 (i.p., 0.5 or 2 mg/kg) or SDZ SER 082 (i.p., 1 mg/kg) was injected twice daily for another 14 days. Whole-cell patch-clamp techniques were used to record ionic currents in freshly isolated ventricular cardiomyocytes. Western blot and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assays were used to assess myocardial apoptosis.3. Expression of 5-HT2B receptors was enhanced in the hypertrophic left ventricle induced by NE overload in vivo. The 5-HT2B receptor antagonist SB 204741 partially reversed cardiac hypertrophy induced by NE overload (P < 0.05) and decreased L-type calcium currents in ventricular cardiomyocytes (P < 0.05). In addition, SB 204741 notably attenuated myocardial apoptosis, as evidenced by downregulation of Bax and caspase 3 (P < 0.05) and upregulation of the anti-apoptotic Bcl-2 protein (P < 0.05).4. In conclusion, the data suggest an involvement of 5-HT2B receptors in the generation of apoptotic events associated with cardiac remodelling during increased adrenergic stimulation.