重组人生长激素对幼年扩张型心肌病模型大鼠心脏结构及功能的改善作用

Improvement in cardiac morphology and function in young rats with dilated cardiomyopathy by recombinant human growth hormone

摘要:

目的 观察重组人生长激素(rhGH)对幼年扩张型心肌病(DCM)模型大鼠左心室形态及功能的影响, 以及其对DCM的改善效果及安全性。方法 将60只Sprague-Dawley雄性大鼠随机分为空白对照组、DCM组和生长激素治疗组(rhGH组), 每组20只。呋喃唑酮(0.25 mg/g)灌胃12周制作DCM模型; rhGH组大鼠给予rhGH腹腔注射(0.15 u/kg), 每日1次, 共12周, DCM组行等量生理盐水替代腹腔注射; 空白对照组不采取任何措施。多普勒超声心动图检测心脏指数, ELISA法检测血清生化指标水平, 多导生理仪检测血流动力学指标, 普通光镜和电镜下观察各组大鼠心脏病理组织学改变, 苦味酸-天狼猩红偏振光法染色检测心肌胶原蛋白水平。结果 与对照组相比, DCM组大鼠均表现出明显心腔扩大, 室壁厚度明显变薄, 缩短分数(FS)和射血分数(EF)下降(P<0.05); rhGH组大鼠心腔容积、室壁厚度、FS和EF等均较DCM组明显改善(P<0.05), 接近对照组水平(P>0.05)。DCM组大鼠各血清生化指标和血流动力学指标水平与对照组相比差异均有统计学意义(P<0.05); 与DCM组相比, 上述指标在rhGH组均得到较大改善(P<0.05), 除胰岛素样生长因子-1(IGF-1)和IGF结合蛋白-3(IGFBP-3)外, 其余指标与对照组相比差异均无统计学意义(P>0.05)。DCM组心肌胶原蛋白ColⅠ/ColⅢ比值高于对照组和rhGH组(P<0.05), 而在对照组和rhGH组间ColⅠ/ColⅢ比值差异无统计学意义(P>0.05)。结论 rhGH对幼年DCM模型大鼠左心室形态及心功能改善具有一定的作用。

Abstract:

Objective To investigate the effects of recombinant human growth hormone (rhGH) on the morphology and function of the left cardiac ventricle in young rats with dilated cardiomyopathy (DCM), and to evaluate the efficacy and safety of rhGH in the treatment of DCM. Methods Sixty male Sprague-Dawley rats were randomly and equally assigned to control group, DCM group, and rhGH group. Furazolidone (0.25 mg/g) was given by gavage for 12 weeks to prepare the DCM model. Rats in the rhGH group received an intraperitoneal injection of rhGH (0.15 U/kg) once per day for 12 weeks, while rats in the DCM group received an equal volume of normal saline instead. Rats in the control group did not receive any treatment. Cardiac indices, serum biochemical parameters, hemodynamic indices, cardiac histopathological changes, and levels of myocardial collagen fibrils in each group were determined using Doppler echocardiography, enzyme-linked immunosorbent assay, multi-channel physiological recorder, light and electron microscopy, and picrosirius red staining plus polarization microscopy, respectively. Results Compared with the control group, rats in the DCM group had significantly increased cardiac chamber size, significantly reduced ventricular wall thickness, and significantly decreased fractional shortening (FS) and ejection fraction (EF) (P<0.05). Rats in the rhGH group had significantly improved cardiac chamber size, ventricular wall thickness, FS, and EF compared with the DCM group (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05). There were significant differences in serum biochemical parameters and hemodynamic indices between the DCM and control groups (P<0.05). Compared with the DCM group, the rhGH group had significantly improved serum biochemical parameters and hemodynamic indices (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05), except for the levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. The DCM group had a significantly higher collagen type I/collagen type III (Col I/Col III) ratio in the myocardium than the control group (P<0.05), and there was no significant difference in the Col I/Col III ratio between the control and rhGH groups (P>0.05). Conclusions rhGH plays a certain role in improvement in the morphology and function of the left cardiac ventricle in young rats with DCM.