Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: 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 (n=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. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68+ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.
目的： 探讨双侧颈上神经节切除对压力负荷型心力衰竭（心衰）小鼠心室重构及心功能的影响。 方法： 健康雄性6周龄C57BL/6小鼠共24只，体重20~25 g。采用随机数字法分为4组，即对照组（n=6，进行假手术）、去神经组（n=6，手术切除双侧颈上神经节）、心衰组［n=6，采用重度胸主动脉缩窄术（sTAB）建立压力负荷型心衰模型］和心衰去神经组（n=6，于sTAB术后2周行双侧颈上神经节切除术）。分别于sTAB术前以及后第2、3、4周行超声心动图检测小鼠心功能。于sTAB术后第4周末处死小鼠，取心肌组织。心肌组织切片行苏木素-伊红（HE）、Masson和免疫组织化学染色进行心肌形态和组织学分析；提取心肌组织蛋白，采用Western blot法检测其酪氨酸羟化酶（TH）、B型利钠肽（BNP）及β1肾上腺素能受体（AR-β1）的蛋白表达水平。 结果： 心衰组和心衰去神经组小鼠sTAB术后第2、3、4周左心室射血分数（LVEF）逐渐减低，术后第4周心衰去神经组小鼠LVEF高于心衰组（P<0.05），而去神经组小鼠各时间点LVEF与对照组比较差异均无统计学意义（P均>0.05）。sTAB术后第4周HE染色结果显示，与对照组比较，去神经组小鼠心肌细胞横截面积差异无统计学意义（P>0.05），心衰组小鼠则较大（P<0.05），而心衰去神经组小鼠较心衰组小（P<0.05）。Masson染色结果显示，对照组和去神经组小鼠心肌组织几乎无蓝染，而心衰组小鼠心肌组织出现大量蓝染，心衰去神经组小鼠蓝染组织少于心衰组。免疫组织化学染色结果显示，去神经组小鼠TH阳性神经纤维密度与对照组比较差异无统计学意义（P>0.05），而心衰组小鼠心肌组织中可见大量TH阳性的神经纤维，心衰去神经组小鼠心肌组织中TH阳性神经纤维的密度较心衰组低（P<0.05）。Western blot结果显示，心衰组小鼠心肌组织中TH蛋白表达水平高于对照组（P<0.05），而心衰去神经组则低于心衰组（P<0.05），且BNP蛋白在各组间表达的差异与TH蛋白相似。与对照组比较，去神经组小鼠AR-β1蛋白表达水平差异无统计学意义（P>0.05），心衰组则较低（P<0.05），而心衰去神经组与心衰组该指标差异无统计学意义（P>0.05）。免疫组织化学染色结果显示，与对照组比较，去神经组小鼠心脏CD68阳性细胞密度差异无统计学意义（P>0.05），心衰组则较高（P<0.05），而心衰去神经组较心衰组低（P<0.05）。 结论： 切除双侧颈上神经节可减小心衰后小鼠心脏交感神经密度，减少巨噬细胞浸润，减轻心室重构，改善心功能。.