Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy
Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy
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去肾神经对缺血性心肌病大鼠心肌纤维化和室性心律失常的影响
DOI：
10.1159/000489653
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发表时间：
2018-05
影响因子：
--
通讯作者：
Shan Qijun
中科院分区：
文献类型：
--
作者：
Zhang Bin;Li Xiaorong;Chen Chu;Jiang Wanying;Lu Dasheng;Liu Qian;Wang Kai;Yan Yuhao;Jiang Zhixin;Geng Jie;Xu Hai;Shan Qijun
背景/目标：探讨去肾神经（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。方法：采用成年SD雄性大鼠，复制心肌梗死（MI）的缺血性心肌病模型。在MI后2周进行RDN/Sham-RDN手术。假手术组（Sham-MI）和假手术组（Sham-RDN）大鼠作为对照组。在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室颤。在PES结束时，收获心脏和肾脏样品。采用免疫荧光标记技术观察心肌梗死边缘区连接蛋白43（Cx43）的分布。Masson三色染色法测定心肌纤维化程度。Western blotting检测转化生长因子β 1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）和Cx43的表达。采用酶联免疫吸附试验（ELISA）检测各组大鼠血清B型利钠肽（BNP）、I型胶原氨基端前肽（PINP）和III型胶原氨基端前肽（PIIINP）水平及肾组织去甲肾上腺素（NE）表达水平。结果如下：与MI组比较，RDN组VA的诱导明显减少（MI+RDN 3/8大鼠vs. MI 8/9大鼠，P < 0.05;对照1/8大鼠），PES减少心肌纤维化（通过胶原体积分数估计）（MI+RDN组31.10 ± 3.97% vs. MI组54.80 ± 16.39%，P < 0.001;对照组4.41 ± 0.92%），抑制TGF-β1（P < 0.01）和α-SMA（P < 0.001）水平，并减弱PINP（MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL，P < 0.001;对照组11.90 ± 4.96 ng/mL）和PIIINP（MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL，P < 0.05;对照组64.69 ± 23.84 ng/mL）水平。RDN还能逆转心肌梗死后Cx43的异常分布和减少（P < 0.01）。结论：RDN可减轻缺血性心肌病大鼠心肌纤维化，抑制VA。
Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: 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. Results: 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). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.
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影响因子：
2.3
作者：
F. Naccarella;G. Lepera;A. Rolli
通讯作者：
F. Naccarella;G. Lepera;A. Rolli
影响因子：
--
作者：
Luo, Qiancheng;Guo, Dongfeng;Jin, Mingming
通讯作者：
Jin, Mingming
影响因子：
2.7
作者：
Godemann, F;Butter, C;Behrens, S
通讯作者：
Behrens, S
影响因子：
--
作者：
Xiao, Junhui;Yu, Kunwu;Zeng, Qiutang
通讯作者：
Zeng, Qiutang
DOI：
10.1161/circinterventions.116.004172
发表时间：
2017-03-01
影响因子：
5.6
作者：
Jackson, Nicholas;Gizurarson, Sigfus;Nanthakumar, Kumaraswamy
通讯作者：
Nanthakumar, Kumaraswamy