粒细胞集落刺激因子对自发性高血压大鼠心室重构的调控

Effect of granulocyte-colony stimulating factor on ventricular remodeling in spontaneously hypertensive rats

关键词:  粒细胞集落刺激因子  高血压  心室重构  大鼠

Key words:  granulocyte-colony stimulating factor  hypertension  ventricular remodeling  rat

摘要:

目的研究早期反复给予大剂量粒细胞集落刺激因子（granulocyte colony stimulating factor, G-CSF)动员骨髄干细胞,对自发性高血压大鼠早期心室重构的调控作用。方法30只10周龄自发性高血压大鼠，随机分为3组，每组10只。G-CSF组连续接受4个周期用药动员骨髄干细胞，1个周期持续14 d,前5 d皮下注射G-CSF 50μg/(kg·d),后9 d不用药物;假性实验组干预药物为生理盐水，注射方法同G-CSF组；空白对照组不用药物。 祠养8周后，进行动物超声心动图检查室间隔厚度（interventricular septal thickness, IVST)和左室短轴收缩率。麻醉条件下解剖取大鼠心室，计算心室质量/体质量,左心室心肌病理切片观察。结果G-CSF组较假性实验组及空白组心室/体质量增加（P＜0.01)，lVST增加（P＜0.05)，左室短轴收缩率明显改善（P＜0.05)。病理结果显示，G-CSF组较假性实验组及空白组心肌纤维排列整齐，心肌肢原容积分数和血管周围肢原面积明显降低（P＜0.05)。结论早期反复大剂量G-CSF动员骨髄干细胞,促进心脏适应性犯厚,提高心肌收缩力，抑制心肌纤维化，减轻不良重构，维持心脏功能。

Abstract:

Objective To study the effect of granulocyte colony stimulating factor (G-CSF) on ventricular remodeling in spontaneously hypertensive rats. Methods Thirty spontaneously hypertensive rats aged 10 weeks were randomly divided into 3 groups with 10 in each group. Group G-CSF received 4 cycles treatment of bone marrow stem cells mobilization with each cycle of 14 d and subcutaneous injection of G-CSF 50μg/(kg·d) was administrated in the first 5 d of the cycle； while Group NS received normal saline and blank control group received no drug. After 8 weeks of feeding, the interventricular septal thickness (IVST) and left ventricular fractional shortening were measured with echocardiography. After the animals were sacrificed, the ventricular weight was measured and the ratio of ventricular/body mass (VW/BW) was calculated, and the myocardium of left ventricule was examined pathologically. Results Compared with NS group and blank group, G-CSF group had higher VW/BW (P<0.01), increased IVST (P<0.05) and left ventricular fractional shortening (P<0.05). Myocardial cells of G-CSF group arranged neatly and collagen volume fraction and perivascular collagen area decreased significantly (P<0.05 ). Conclusion Early repeated administration of high dose G-CSF can mobilize bone marrow stem cells，promote adaptive cardiac hypertrophy，enhance myocardial contractility，inhibit myocardial fibrosis，reduce adverse remodeling and maintain cardiac function.