Reversal of isoprenaline-induced cardiac remodeling by rutaecarpine via stimulation of calcitonin gene-related peptide production
Reversal of isoprenaline-induced cardiac remodeling by rutaecarpine via stimulation of calcitonin gene-related peptide production
复制标题
吴茱萸碱通过刺激降钙素基因相关肽的产生逆转异丙肾上腺素诱导的心脏重塑
DOI：
10.1139/y10-067
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发表时间：
2010-10-01
影响因子：
2.1
通讯作者：
Li, Yuan-Jian
中科院分区：
文献类型：
--
作者：
Li, Jian-Zhe;Peng, Jun;Li, Yuan-Jian
辣椒素敏感的感觉神经功能障碍参与心脏重塑，并且已经显示吴茱萸次碱通过激活感觉神经对心脏功能发挥有益作用。本研究旨在探讨吴茱萸次碱对心脏重塑的潜在抑制作用及其机制。用异丙肾上腺素（5mg/kg/d，s.c.）10天吴茱萸次碱（10或40 mg/kg，i.g.）与异丙肾上腺素合用，观察吴茱萸次碱对心脏重构的影响。超声心动图分析后，采集血液定量测定降钙素基因相关肽（CGRP），分离背根神经节测定CGRP mRNA表达，并称重保存心脏以评价细胞凋亡和肥大相关参数。异丙肾上腺素显著增加左心室重量与体重的比值，心肌细胞的横截面积，心肌细胞凋亡和胶原沉积伴随着减少CGRP的产生，这是逆转的吴茱萸次碱治疗。吴茱萸次碱的有益作用被辣椒素预处理减弱，辣椒素选择性地耗尽CGRP。这些结果表明，吴茱萸次碱能够逆转异丙肾上腺素诱导的心脏重塑，通过刺激CGRP的生产。
Dysfunction of capsaicin-sensitive sensory nerves is involved in cardiac remodeling, and rutaecarpine has been shown to exert a beneficial effect on cardiac function through activating the sensory nerves. This study was conducted to explore the potential inhibitory effect of rutaecarpine on cardiac remodeling and the underlying mechanisms. A rat cardiac remodeling model was established by injection of isoprenaline (5 mg/kg per day, s.c.) for 10 days. Rutaecarpine (10 or 40 mg/kg, i.g.) was coadministrated with isoprenaline to evaluate the effect of rutaecarpine on cardiac remodeling. After echocardiographic analysis was performed, blood samples were collected to quantify calcitonin gene-related peptide (CGRP), dorsal root ganglia were isolated for examining CGRP mRNA expression, and the hearts were weighed and saved for evaluating the parameters related to apoptosis and hypertrophy. Isoprenaline significantly increased the ratio of left ventricle weight to body weight, the cross-sectional area of cardiomyocytes, cardiac apoptosis, and collagen deposition concomitantly with decreased CGRP production, which were reversed by rutaecarpine treatment. The beneficial effects of rutaecarpine were attenuated by pretreatment with capsaicin, which selectively depleted CGRP. These results suggest that rutaecarpine was able to reverse isoprenaline-induced cardiac remodeling through stimulating CGRP production.