Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Department of Cardiology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei 441300, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5091-5098. doi: 10.3892/mmr.2017.7255. Epub 2017 Aug 16.
The aim of the present study was to determine if renal sympathetic denervation (RSD) may alleviate isoproterenol-induced left ventricle remodeling, and to identify the underlying mechanism. A total of 70 rats were randomly divided into control (n=15), sham operation (n=15), heart failure (HF) with sham operation (HF + sham; n=20) and HF with treatment (HF + RSD; n=20) groups. The HF model was established by subcutaneous injection of isoproterenol; six weeks later, 1eft ventricular internal diameter at end‑systole (LVIDs), left ventricular systolic posterior wall thickness (LVPWs), 1eft ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured. Plasma norepinephrine (NE), angiotensin II (Ang II) and aldosterone (ALD) levels were measured by ELISA. Myocardial collagen volume fraction (CVF) was determined by Masson's staining. Reverse transcription‑quantitative polymerase chain reaction was used to determine the mRNA expression levels of ventricular transforming growth factor‑β (TGF‑β), connective tissue growth factor (CTGF) and microRNAs (miRs), including miR‑29b, miR‑30c and miR‑133a. The results demonstrated that LVIDs and LVPWs in the HF + RSD group were significantly decreased compared with the HF + sham group. By contrast, LVFS and LVEF in the HF + RSD group were significantly increased compared with the HF + sham group. RSD significantly reduced the levels of plasma NE, Ang II and ALD. CVF in the HF + RSD group was reduced by 38.1% compared with the HF + sham group. Expression levels of TGF‑β and CTGF were decreased, whereas those of miR‑29b, miR‑30c and miR‑133a were increased, in the HF + RSD group compared with the HF + sham group. These results indicated that RSD alleviates isoproterenol‑induced left ventricle remodeling potentially via downregulation of TGF‑β/CTGF and upregulation of miR‑29b, miR‑30c and miR‑133a. RSD may therefore be an effective non‑drug therapy for the treatment of heart failure.
本研究旨在探讨肾脏去交感神经支配（RSD）是否可缓解异丙肾上腺素诱导的左心室重构，并确定其潜在机制。将 70 只大鼠随机分为对照组（n=15）、假手术组（n=15）、心力衰竭（HF）+假手术组（HF+sham；n=20）和 HF+治疗组（HF+RSD；n=20）。通过皮下注射异丙肾上腺素建立 HF 模型；6 周后，测量左心室收缩末期内径（LVIDs）、左心室收缩后壁厚度（LVPWs）、左心室射血分数（LVEF）和左心室短轴缩短率（LVFS）。通过 ELISA 法测定血浆去甲肾上腺素（NE）、血管紧张素 II（Ang II）和醛固酮（ALD）水平。Masson 染色法测定心肌胶原容积分数（CVF）。采用逆转录-定量聚合酶链反应（RT-qPCR）测定心室转化生长因子-β（TGF-β）、结缔组织生长因子（CTGF）和 microRNA（miR），包括 miR-29b、miR-30c 和 miR-133a 的 mRNA 表达水平。结果显示，HF+RSD 组的 LVIDs 和 LVPWs 明显低于 HF+sham 组。相反，HF+RSD 组的 LVFS 和 LVEF 明显高于 HF+sham 组。RSD 显著降低了血浆 NE、Ang II 和 ALD 水平。HF+RSD 组的 CVF 比 HF+sham 组降低了 38.1%。HF+RSD 组 TGF-β和 CTGF 的表达水平降低，而 miR-29b、miR-30c 和 miR-133a 的表达水平升高。这些结果表明，RSD 通过下调 TGF-β/CTGF 和上调 miR-29b、miR-30c 和 miR-133a 缓解异丙肾上腺素诱导的左心室重构。因此，RSD 可能是心力衰竭治疗的一种有效非药物治疗方法。
