摘要
目的探讨应用粒细胞集落刺激因子(G-CSF)动员骨髓干细胞对兔急性心肌梗死的治疗作用及较佳的治疗时间窗。方法33只健康大耳兔开胸结扎左室后支中下段建立心肌梗死模型后,随机分为对照组(9只)、早期动员组(12只)、延迟动员组(12只)。对照组于心肌梗死后第3小时皮下注射生理盐水;早期动员组和延迟动员组分别于心肌梗死后第3小时和第7天开始皮下注射G-CSF,每天1次,每次20μg/kg,连续5d。模型制备前和制备成功后7、28d行超声心动图检查,测量左室舒张末期内径(Dd)、收缩末期内径(Ds)并计算左室短轴缩短率(Dd-Ds)/Dd,测量左室后壁厚度和左室射血分数;心肌梗死后28d取心脏做心肌组织病理学检查和内皮细胞Ⅷ因子免疫组织化学染色,计算心肌梗死总面积占左室总面积百分比和心肌毛细血管内皮细胞Ⅷ因子染色阳性率。结果心肌梗死后28d,延迟动员组兔心脏结构与功能均有明显改善,左室短轴缩短率(0.30±0.05)、左室后壁厚度(0.19cm±0.02cm)和左室射血分数(56.7%±3.4%)均大于对照组(分别为0.20±0.02、0.17cm±0.02cm、47.7%±3.5%,均P<0.05);心肌梗死面积占左室总面积的(18±3)%,低于对照组的(22±2)%(P<0.05)和早期动员组的(21±2)%(P<0.05);梗死区心肌毛细血管内皮细胞Ⅷ因子染色阳性率(90.8%)明显高于对照组(25.2%,P<0.01)和早期动员组(72.0%,P<0.05)。实验结束时,动物病死率延迟动员组为16.7%(2/12),早期动员组25.0%(3/12),对照组33.3%(3/9),延迟动员组与对照组比较,差异有统计学意义(P<0.05)。结论骨髓干细胞动员治疗心肌梗死可明显改善心脏功能;心肌梗死后7d是进行骨髓干细胞动员的较佳时间窗。
Objective To investigate the effect of granulocyte-colony stimulating factor (G-CSF) on the mobilization of marrow stem cells in rabbits with acute myocardial infarction, and its optimal therapeutic time window. Methods A total of 33 healthy rabbits were used to establish the models of myocardial infarction by opening the chest and ligating the posterior left ventricular branch. The rabbits were randomly divided into three groups: control group (9 animals), early mobilized group (12), and late mobilized group (12). The rabbits in the control group were injected with physiological saline subcutaneously 3 hours after myocardial infarction. While the animals in the early and late mobilized groups were injected with G-CSF cutaneously 3 and 7 hours after the myocardial infarction respectively (20 μg·kg-1·d-1 × 5 day). Echocardiography was performed before and 7 and 28 days after the establishment of the myocardial infarction models to measure the end-diastolic inner diameter of the left ventricle (Dd), end-systolic inner diameter of the left ventricle (Ds), shortening fraction of the left ventricle (Dd-Ds)/Dd, thickness of the posterior left ventricular wall, and the ejection fraction of the left ventricle. The myocardial tissues were obtained 28 days after the myocardial infarction and stained with HE and immunostained with endothelial cell factorⅧ-related antigen monoclonal antibody. The ratio of infracted area to the total left ventricular area and the rate of capillaryendothelial cells positive for factor Ⅷ were calculated. Results In the late mobilized group, the cardiac structure and function was improved obviously 28 days after myocardial infarction, the (Dd-Ds)/Dd (0.30 ± 0.05), thickness of the posterior left ventricular wall (0.19 cm ± 0.02 cm), and the ejection fraction of the left ventricle (56.7% ± 3.4%) were all significantly higher than those in the control group (0.20 ± 0.02, 0.17 cm ± 0.02 cm, 47.7% ± 3.5% , respectively, P < 0.05). The ratio of infracted area to the total left ventricular area in the late mobilized group was (18 ± 3)%, which was significantly lower than that in the control (22% ± 2%) and early mobilized group (21% ± 2%) (both P < 0.05). The rate of capillary endothelial cells positive for factor Ⅷ in the late mobilized group (90.8%) was significantly higher than that in the control group (25.2%, P < 0.01) and early mobilized group (72.0%, P < 0.05). At the end of the study, the death rate in the late mobilized group was 16.7% (2/12), which is significantly lower than that in the control 33% (3/9), (P < 0.05). And in the early mobilized group, the rate was 25.0% (3/12). Conclusions G-CSF-mobilized bone marrow stem cells can obviously improve the cardiac function after myocardial infarction. The optimal therapeutic time window is 7 days after infarction.
出处
《中国医药生物技术》
CSCD
2007年第4期281-285,封面,共6页
Chinese Medicinal Biotechnology
关键词
粒细胞集落刺激因子
心肌梗死
模型
动物
免
Granulocyte colony-stimulating factor
Myocardial infarction
Models, animal
Robbits
