摘要
目的:探讨碱性成纤维细胞生长因子(basic fibroblast growth factor,b FGF)对心肌梗死小鼠心脏的保护作用及机制。方法:采用异氟烷麻醉C57/B6小鼠(8~12周龄)后,侧开胸结扎冠状动脉左前降支,建立小鼠心肌梗死模型;设立假手术组为对照,心肌梗死模型小鼠随机分为心梗组和bFGF给药组,其中bFGF组小鼠心梗7d后给予5μg b FGF隔天腹腔注射给药;在小鼠心梗第28天时采用心脏多普勒超声检测心功能,以左室舒张末期内径、左室收缩末期内径、左心室射血分数和左心室短轴缩短分数评价心脏功能改变;28 d后处死小鼠,行病理切片观察心肌纤维化程度和心肌梗死区内血管新生的情况;Western blot检测血管新生指标。结果:bFGF给药组小鼠心肌纤维化程度较心梗模型组明显减少;第28天行超声心动图检查结果示,心梗组小鼠心功能较假手术组差,而bFGF给药组小鼠心功能与心梗组比较有明显的改善;小鼠心肌病理切片免疫荧光观察结果发现,bFGF给药组心肌梗死区的新生血管比心梗组明显增多;Western blot实验表明,bFGF能够激活AKT/HIF-1α/VEGF通路。结论:隔天腹腔注射bFGF能够减少心肌梗死小鼠心肌纤维化,改善心功能。bFGF可能通过AKT/HIF-1α/VEGF信号通路促进血管新生,从而保护心脏。
AIM:To investigate the protective effect of basic fibroblast growth factor(bFGF)on the heart of mice with myocardial infarction and its mechanism.METHODS:The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6mice(8~12weeks old)after lateral thoracotomy.The mice were divided into sham operation group,myocardial infarction group and bFGF administration group.bFGF at0.5μg was intraperitoneally injected on alternate days after myocardial infarction for7d.Cardiac Doppler ultrasonography was used to detect cardiac function after myocardial infarction for28d,and left ventricular end-diastolic diameter,left ventricular end-systolic diameter,left ventricular ejection fraction and left ventricular shortening fraction(LVFS)were used to evaluate cardiac function.After myocardial infarction for28d,the mice were sacrificed and the hearts were collected for preparing pathological sections.The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed.Western blot was used to detect the indicators of angiogenesis.RESULTS:The results of Masson staining showed that bFGF administration significantly reduced myocardial fibrosis at28d after myocardial infarction.Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group,and bFGF administration significantly improved cardiac functions.Immunofluorescence staining showed that neovascularization in myocardial infarction area of bFGF administration group was more than that in myocardial infarction group.The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway.CONCLUSION:Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice.bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.
作者
沈丹萍
戈东辉
陈显达
吴雨晴
李磊
褚茂平
SHEN Danping;GE Donghui;CHEN Xianda;WU Yuqing;LI Lei;CHU Maoping(The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, The Children’s Heart Center, The Institute of Heart Development and Translational Medicine, Wenzhou Medical University, Wenzhou 325027 , China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第1期47-51,共5页
Chinese Journal of Pathophysiology
基金
国家卫生和计划生育委员会科研基金资助项目(No.WKJ-ZJ-1725)
