Hou Xu Wei, Son Ja, Wang Yang, Ru Yong Xin, Lian Qing, Majiti Wuliya, Amazouzi A, Zhou Yu Ling, Wang Pei Xian, Han Zhong Chao
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 30020, China.
Cardiovasc Drugs Ther. 2006 Apr;20(2):85-91. doi: 10.1007/s10557-006-7652-9.
Cardiomyocyte apoptosis reportedly participates in the occurrence and progression of dilated cardiomyopathy (DCM). Recent studies have shown that granulocyte colony-stimulating factor (G-CSF) enhances bone marrow cells migration to the damaged heart in the DCM model and improves the ultrastructure of the cardiomyocyte in adriamycin (ADR) induced DCM. However, its influence on cardiac pump function and cardiomyocyte apoptosis has not been studied.
Wistar Rats were randomly grouped into control, ADR, ADR+PBS, ADR+G-CSF group (n = 10). ADR (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally in all rats except the control group. After 2 weeks, the rats in ADR+G-CSF group were injected with G-CSF (50 microg/kg/day for 8 days) subcutaneously. Cardiac function was evaluated by echocardiogram and cardiac catheterization after 4 weeks. Cardiomyocytes apoptosis and apoptosis-related protein Fas were detected by in situ terminal deoxynucleotidyl transferase assay (TUNEL method) and Western blot, respectively.
The ADR and ADR+PBS groups showed significant deteriorations of left ventricular functions and high cardiomyocyte apoptosis index, as well as high Fas expressions. Meanwhile, the ADR+G-CSF group showed significant improvement in LV function, inhibition of cardiomyocyte apoptosis compared with the ADR and ADR+Phosphate-Buffered Saline PBS group. The Fas protein expression was remarkably attenuated as well.
Our results suggest that administration of G-CSF inhibited cardiomyocyte apoptosis and Fas protein expression and contributes to improving cardiac pump function in vivo in ADR induced DCM rat model.
据报道，心肌细胞凋亡参与扩张型心肌病（DCM）的发生和发展。最近的研究表明，粒细胞集落刺激因子（G-CSF）可增强骨髓细胞向DCM模型中受损心脏的迁移，并改善阿霉素（ADR）诱导的DCM中心肌细胞的超微结构。然而，其对心脏泵功能和心肌细胞凋亡的影响尚未见研究。
将Wistar大鼠随机分为对照组、ADR组、ADR+PBS组、ADR+G-CSF组（n = 10）。除对照组外，所有大鼠均腹腔注射ADR（2.5 mg/kg，共6次，持续2周）。2周后，ADR+G-CSF组大鼠皮下注射G-CSF（50μg/kg/天，共8天）。4周后通过超声心动图和心脏导管检查评估心功能。分别采用原位末端脱氧核苷酸转移酶测定法（TUNEL法）和蛋白质免疫印迹法检测心肌细胞凋亡及凋亡相关蛋白Fas。
ADR组和ADR+PBS组左心室功能显著恶化，心肌细胞凋亡指数高，Fas表达也高。同时，与ADR组和ADR+磷酸盐缓冲液（PBS）组相比，ADR+G-CSF组左心室功能显著改善，心肌细胞凋亡受到抑制。Fas蛋白表达也明显减弱。
我们的结果表明，在ADR诱导的DCM大鼠模型中，给予G-CSF可抑制心肌细胞凋亡和Fas蛋白表达，并有助于改善体内心脏泵功能。
