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双侧颈上神经节切除术减轻压力超负荷心力衰竭小鼠的心脏重塑并改善心脏功能

[Bilateral superior cervical ganglionectomy attenuates cardiac remodeling and improves cardiac function in pressure-overloaded heart failure mice].

作者信息

Li G R, Li H, Lyu Z, Chen Z, Wang Y G

机构信息

Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Department of Internal Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2021 Apr 24;49(4):345-352. doi: 10.3760/cma.j.cn112148-20200603-00458.

Abstract

To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor β1 (AR-β1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-β1. Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (<0.05), which was similar between denervated HF group and control group (>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (<0.05). IHC showed that TH+nerves and CD68 macrophages were significantly increased in HF mice as compared to control mice (<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (<0.05), which was not affected by denervation (>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (<0.05), whereas this difference was diminished in denervated HF group (>0.05). Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.

摘要

探讨双侧颈上神经节切除术对压力超负荷型心力衰竭(HF)小鼠心脏重塑及功能的影响。通过严重胸主动脉缩窄(sTAB)建立压力超负荷型HF小鼠模型。在sTAB术后2周进行双侧颈上神经节切除术(SCGx)。将24只6周龄雄性C57BL/6小鼠随机分为4组(每组=6只):对照组:假手术sTAB+假手术SCGx;去神经组:假手术sTAB+SCGx;HF组:sTAB+假手术SCGx;去神经HF组:sTAB+SCGx。分别在sTAB术后第0、1、2和4周通过超声心动图测量心脏功能。在第4周结束时处死所有小鼠并采集心脏组织。进行苏木精-伊红(HE)和Masson染色。进行酪氨酸羟化酶(TH)、肾上腺素能受体β1(AR-β1)和CD68的免疫组织化学染色(IHC)。采用蛋白质印迹法测定TH、B型利钠肽(BNP)和AR-β1的蛋白表达水平。HF组左心室射血分数(LVEF)持续下降。去神经HF组和对照组在各个时间点的LVEF相似(>0.05)。在第4周结束时,去神经HF组的LVEF显著高于HF组(<0.05)。HE染色显示,HF组心肌细胞横截面积显著大于对照组和去神经HF组(<0.05),而去神经HF组和对照组之间相似(>0.05)。Masson染色显示,去神经HF组的纤维化水平显著低于HF组(<0.05)。IHC显示,与对照小鼠相比,HF小鼠中TH+神经和CD68巨噬细胞显著增加(<0.05),而在去神经HF组中这种变化消失。与对照组相比,HF组AR-β1显著下调(<0.05),去神经对此无影响(>0.05)。蛋白质印迹法表明,与对照组相比,HF组TH和BNP的表达水平显著升高(<0.05),而在去神经HF组中这种差异减小(>0.05)。双侧颈上神经节切除术可减少压力超负荷衰竭心脏中的交感神经支配和巨噬细胞浸润,从而减轻心脏重塑并改善心脏功能。

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