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

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)动员骨髓干细胞,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个周期用药动员骨髓干细胞,1个周期持续14 d,前5 d皮下注射G-CSF50μg/(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。饲养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),IVST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,GCSF组较假性实验组及空白组心肌纤维排列整齐,心肌胶原容积分数和血管周围胶原面积明显降低(P<0.05)。结论早期反复大剂量G-CSF动员骨髓干细胞,促进心脏适应性肥厚,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。

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 w eeks w ere randomly divided into 3 groups w ith 10 in each group. Group G-CSF received 4 cycles treatment of bone marrow stem cells mobilization w ith each cycle of 14 d and subcutaneous injection of G-CSF 50 μg /（ kg·d） w as administrated in the first 5 d of the cycle; w hile Group NS received normal saline and blank control group received no drug. After 8 w eeks of feeding, the interventricular septal thickness（ IVST） and left ventricular fractional shortening w ere measured w ith echocardiography. After the animals w ere sacrificed,the ventricular w eight w as measured and the ratio of ventricular / body mass（ VW / BW） w as calculated,and the myocardium of left ventricule w as examined pathologically. Results Compared w ith NS group and blank group,G-CSF group had higher VW / BW（ P ＆lt; 0. 01）,increased IVST（ P ＆lt; 0. 05） and left ventricular fractional shortening（ P ＆lt; 0. 05）. Myocardial cells of G-CSF group arranged neatly and collagen volume fraction and perivascular collagen area decreased significantly（ P ＆lt; 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.