Early use of granulocyte colony stimulating factor improves survival in a rabbit model of chronic myocardial ischemia

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• 作者：Qingbin Zhao ; MD^a ; ^{zhaoqingbin05@163.com} ; Chaofeng Sun ; PhD^a ; Xin Xu ; MD^b ; Juan Zhou ; PhD^c ; Yue Wu ; PhD^a ; Yuling Tian ; PhD^a ; Aiqun Ma ; PhD^a ; Zhiquan Liu ; PhD^a
• 关键词：Myocardial ischemia ; G-CSF ; Neovascularization ; Apoptosis
• 刊名：Journal of Cardiology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：61
• 期：1
• 页码：87-94
• 全文大小：1157 K

文摘

Background

Granulocyte colony stimulating factor (G-CSF) improves the survival of animals with myocardial infarction by inducing bone marrow stem cell mobilization and homing to infarcted areas. However, its precise mechanisms and direct effects on the ischemic myocardium remain unclear. In this study we investigated the direct effects and mechanisms of G-CSF in a rabbit model of chronic myocardial ischemia.

Methods

Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits. Rabbits were subcutaneously injected with 10 ¦Ìg/kg of G-CSF (G-CSF group) or saline (control group) for 6 days after myocardial ischemia. Direct effects of G-CSF were analyzed by immunohistochemistry and terminal dUTP nick end-labeling (TUNEL).

Results

Rabbits in the G-CSF group exhibited 75 % survival compared to 40 % in the control group (p < 0.05). Immunohistochemistry of the ischemic myocardium showed increased homing of CD34+ cells on day 7 post-surgery and more vessels on day 28 post-surgery by anti-von Willebrand factor staining in the G-CSF group compared with the control group. Furthermore, an increased percentage of CD34+ cells were observed in peripheral blood and upregulation of vascular endothelial growth factor expression in ischemic tissue in the G-CSF group compared with the control group. TUNEL showed that the apoptotic index in the ischemic myocardium decreased in the G-CSF group compared with the control group on day 28 post-surgery.

Conclusions

In addition to increasing stem cell mobilization and homing to ischemic myocardium, G-CSF treatment after myocardial ischemia improves survival by accelerating neovascularization and reducing apoptosis.