Zhang Bin, Li Xiaorong, Chen Chu, Jiang Wanying, Lu Dasheng, Liu Qian, Wang Kai, Yan Yuhao, Jiang Zhixin, Geng Jie, Xu Hai, Shan Qijun
Cell Physiol Biochem. 2018;46(6):2471-2479. doi: 10.1159/000489653. Epub 2018 May 5.
BACKGROUND/AIMS: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy.
An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague-Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson's trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine.
Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01).
RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.
背景/目的：研究肾去神经支配（RDN）对缺血性心肌病大鼠心肌纤维化和室性心律失常（VA）的影响。
采用成年雄性Sprague-Dawley大鼠制作心肌梗死（MI）诱导的缺血性心肌病模型。在MI后2周进行RDN/假手术RDN操作。假MI和假RDN大鼠作为对照组。RDN后4周，在所有3组（MI+RDN组、MI组和对照组）中使用程序电刺激（PES）诱导VA，包括室性心动过速和心室颤动。PES结束时，采集心脏和肾脏样本。采用免疫荧光标记法研究梗死边缘区连接蛋白43（Cx43）的分布。采用Masson三色染色法测定心脏纤维化程度。进行蛋白质免疫印迹法检测转化生长因子β1（TGF-β1）、α平滑肌肌动蛋白（α-SMA）和Cx43的表达。采用酶联免疫吸附测定（ELISA）法检测血清B型利钠肽（BNP）水平以及I型和III型胶原氨基末端前肽（分别为PINP和PIIINP）水平，同时检测肾脏去甲肾上腺素的表达水平。
与MI组相比，RDN显著降低了PES诱导VA的易感性（MI+RDN组8只大鼠中有3只诱发VA，MI组9只大鼠中有8只诱发VA，P<0.05；对照组8只大鼠中有1只诱发VA），通过胶原容积分数评估，心肌纤维化程度降低（MI+RDN组为31.10±3.97%，MI组为54.80±16.39%，P<0.001；对照组为4.41±0.92%），TGF-β1（P<0.01）和α-SMA（P<0.001）水平受到抑制，PINP（MI+RDN组为41.44±10.10 ng/mL，MI组为95.49±24.83 ng/mL，P<0.001；对照组为11.90±4.96 ng/mL）和PIIINP（MI+RDN组为82.12±30.79 ng/mL，MI组为124.60±26.64 ng/mL，P<0.05；对照组为6[X]69±23.84 ng/mL）水平也降低。此外，RDN逆转了Cx43在心肌中的异常分布及其因MI损伤导致的减少（P<0.01）。
在缺血性心肌病大鼠模型中，RDN可减轻心肌纤维化并抑制VA。
