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目的探讨粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)对压力超负荷引起的心室重构和心力衰竭发生发展的影响及其机制。方法实验动物分成7组:PBS组小鼠(PBS组)、替米沙坦组小鼠(ST组)、G-CSF(A)组小鼠(GA组)、G-CSF(B)组小鼠(GB组)、G-CSF +替米沙坦组小鼠(GT组)、替米沙坦+G-CSF组小鼠(TG组)和假手术组小鼠(sham组)。小鼠经缩窄升主动脉后,在不同时间皮下注射G-CSF或(和)替米沙坦,每周做心脏超声检测心脏功能和形态变化,分别于第1周、2周和4周末测量有侧颈动脉压后取材,用HE染色、Masson三色染色观察心脏形态变化,用Western blotting检测血管内皮生长因子(vascular endothelial growth factor,VEGF)和RT-PCR检测缺氧诱导因子1(hypoxia-inducible factorl,HIF-1)、p53mRNA的表达情况。结果(1)在0～14 d,缩窄升主动脉的小鼠心室擘厚度值逐渐升高达高峰,14～28 d PBS组厚度逐渐降低,同时伴有左室射血分数的下降,而给予G-CSF皮下注射的小鼠未见有降低,也未见有射血分数的下降;(2)同PBS组比较,VEGF蛋白、HIF-1mRNA表达存给予G-CSF皮下注射的小鼠显著升高,而p53mRNA表达、心脏纤维化程度和死亡率在给予G-CSF组显著降低。结论G-CSF通过调控血管新生,改善了压力超负荷引起的心室重构和心力衰竭,其中调控HIF-1的表达可能起着重要的作用。
Objective To investigate the effects of granulocyte colony stimulating factor (G-CSF) on the development of ventricular remodeling and heart failure induced by pressure overload and its mechanism. Methods The experimental animals were divided into 7 groups: PBS group (PBS group), telmisartan group (ST group), G-CSF group (GA group) and G-CSF group (GB group), G-CSF + telmisartan group (GT group), telmisartan + G-CSF group (TG group) and sham operation group (sham group). After narrowing the ascending aorta, mice were injected with G-CSF or (and) telmisartan subcutaneously at different times, and their cardiac function and morphological changes were measured weekly by week for the first week, the second week and the fourth week respectively The carotid artery pressure was measured before and after the treatment. The morphological changes of the heart were observed by HE staining and Masson trichrome staining. The expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 -inducible factorl, HIF-1), p53 mRNA expression. Results (1) From 0 to 14 days, the thickness of ventricular tachycardia in ascending aorta increased gradually to the peak, the thickness of PBS group gradually decreased from 14 to 28 days, accompanied by the decrease of left ventricular ejection fraction, G-CSF subcutaneously injected mice showed no decrease and no decrease of ejection fraction. (2) Compared with PBS group, the expression of VEGF protein and HIF-1mRNA in mice subcutaneously injected with G-CSF significantly increased High, whereas p53 mRNA expression, cardiac fibrosis and mortality were significantly reduced in the G-CSF group. Conclusions G-CSF can improve ventricular remodeling and heart failure induced by pressure overload by regulating angiogenesis. The regulation of HIF-1 expression may play an important role.