小青龙汤通过调节心脏交感神经支配失衡维持盐敏感大鼠射血分数降低型心力衰竭时的心脏功能。
Xiao-Qing-Long-Tang Maintains Cardiac Function during Heart Failure with Reduced Ejection Fraction in Salt-Sensitive Rats by Regulating the Imbalance of Cardiac Sympathetic Innervation.
作者信息
Li Zhaoyu, Wang Yongcheng, Jiang Yuehua, Ma Dufang, Jiang Ping, Zhou Guofeng, Yang Jinlong, Dong Feng, Zhao Hengyi, Zhang Yimei, Li Xiao
机构信息
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China.
出版信息
Evid Based Complement Alternat Med. 2020 Nov 24;2020:9467271. doi: 10.1155/2020/9467271. eCollection 2020.
OBJECTIVE
The anatomical and functional imbalances of sympathetic nerves are associated with cardiovascular disease progression. Xiao-Qing-Long-Tang (XQLT), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia for thousands of years. We determined the effect of XQLT in maintaining cardiac function during heart failure with reduced ejection fraction (HFrEF) with respect to its neurobiological effects in salt-sensitive rats.
METHODS
Dahl salt-sensitive (DS) rats were fed a high-salt diet to establish an HFrEF model and were divided into model (DS, administered normal saline) and XQL groups (administrated XQLT) randomly, with SS-13BN rats being used as the control. The bodyweight and blood pressure of rats were observed regularly. Electrocardiogram, echocardiography, and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined to assess cardiac function. The sympathetic tune and myocardial morphological changes were evaluated. Western blot and qRT-PCR were used to assay the expression of the nerve growth factor (NGF) and leukemia inhibitory factor (LIF). Tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43) were assayed to confirm sympathetic remodeling. The micromorphological changes in cardiac sympathetic nerve endings were observed by transmission electron microscopy.
RESULTS
Four weeks after XQLT treatment, cardiac function and bodyweight were higher and blood pressure was lower than that of the DS group. Myocardial noradrenaline (NA) increased, while the plasma NA level decreased significantly. The morphology demonstrated that XQLT significantly alleviated myocardial damage. XQLT decreased the expression of LIF, increased the expression of NGF, enhanced the TH+/GAP43+ and TH+/CHAT + positive nerve fiber density, and improved the TH and GAP43 protein expression, but had no effect on CHAT. Moreover, XQLT improved the micromorphology of sympathetic nerve endings in the myocardium.
CONCLUSION
XQLT maintains cardiac function during HFrEF in salt-sensitive rats, in part, by regulating the imbalance of cardiac sympathetic innervation.
目的
交感神经的解剖和功能失衡与心血管疾病进展相关。小青龙汤（XQLT）是一种古老的中药配方，在东亚用于治疗心血管疾病已有数千年历史。我们研究了XQLT在射血分数降低的心力衰竭（HFrEF）期间维持心脏功能的作用及其对盐敏感大鼠的神经生物学效应。
方法
给 Dahl 盐敏感（DS）大鼠喂食高盐饮食以建立 HFrEF 模型，并随机分为模型组（DS，给予生理盐水）和 XQL 组（给予 XQLT），以 SS-13BN 大鼠作为对照。定期观察大鼠的体重和血压。测定心电图、超声心动图和血浆 N 末端 B 型利钠肽原（NT-proBNP）以评估心脏功能。评估交感神经调节和心肌形态学变化。采用蛋白质免疫印迹法（Western blot）和定量逆转录聚合酶链反应（qRT-PCR）检测神经生长因子（NGF）和白血病抑制因子（LIF）的表达。检测酪氨酸羟化酶（TH）、胆碱乙酰转移酶（CHAT）和生长相关蛋白 43（GAP43）以确认交感神经重塑。通过透射电子显微镜观察心脏交感神经末梢的微观形态变化。
结果
XQLT 治疗 4 周后，心脏功能和体重高于 DS 组，血压低于 DS 组。心肌去甲肾上腺素（NA）增加，而血浆 NA 水平显著降低。形态学显示 XQLT 显著减轻心肌损伤。XQLT 降低 LIF 表达，增加 NGF 表达，提高 TH+/GAP43+和 TH+/CHAT+阳性神经纤维密度，改善 TH 和 GAP43 蛋白表达，但对 CHAT 无影响。此外，XQLT 改善了心肌交感神经末梢的微观形态。
结论
XQLT 在盐敏感大鼠的 HFrEF 期间维持心脏功能，部分是通过调节心脏交感神经支配的失衡来实现的。
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