NICD/Hes1影响心肌梗死后小鼠缺血心肌的血管新生  

NICD/Hes1 affects angiogenesis in the ischemic myocardium of myocardial infarction mice

作　　者：卢鹏飞 施伟丽 Lu Pengfei;Shi Weili(Cardiovascular Division,Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,Henan Province,China;The Second Clinical Medical College of Henan University of Chinese Medicine(Henan Hospital of Traditional Chinese Medicine),Zhengzhou 450002,Henan Province,China)

机构地区：[1]河南中医药大学第三附属医院心血管科,河南省郑州市450003 [2]河南中医药大学第二临床医学院(河南省中医院),河南省郑州市450002

出　　处：《中国组织工程研究》2023年第23期3635-3639,共5页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年项目(81803771),项目负责人:施伟丽。

摘　　要：背景:心肌缺血是心肌梗死后心功能受损的主要原因之一,Notch通路参与血管新生过程,但其下游分子Notch受体胞内部分(Notch intracellular domain,NICD)/Hes1在心肌梗死后缺血心肌血管新生中发挥何种作用,研究尚少。目的:借助Notch γ分泌酶抑制剂RO4929097,探讨NICD/Hes1对心肌梗死后小鼠心功能及缺血心肌血管新生的影响。方法:按随机数字表法将C57BL/6小鼠分为假手术组、模型组和RO4929097组,每组10只,后2组C57BL/6小鼠通过结扎左前降支冠状动脉建立心肌梗死模型,RO4929097组小鼠术后第2天按10 mg/(kg·d)每天灌胃1次,假手术组和模型组小鼠给予等体积生理盐水,灌胃20 d。第21天超声检测小鼠左室射血分数,马松染色观察心肌梗死面积及病理组织学变化,免疫荧光法检测缺血心肌CD31水平,酶联免疫吸附法检测血清血管内皮生长因子和碱性成纤维细胞生长因子水平,免疫蛋白印迹技术检测心肌组织缺氧诱导因子1α、心肌营养素1及NICD、Hes1蛋白表达量。结果与结论:(1)模型组小鼠左室射血分数较假手术组显著降低(P <0.001),与模型组比较,RO492909组左室射血分数降低更明显(P <0.05);(2)马松染色后,模型组及RO492909组小鼠梗死面积较假手术组显著增加(P<0.001),RO492909组梗死面积较模型组增加明显(P<0.05);(3)模型组小鼠心肌CD31平均吸光度值较假手术组升高明显(P<0.001),RO492909组CD31平均吸光度值较模型组明显降低(P<0.001);(4)模型组、RO4929097组小鼠血清血管内皮生长因子水平较假手术组明显升高(P<0.05),RO492909组血管内皮生长因子较模型组升高明显(P <0.01);(5)模型组小鼠心肌组织缺氧诱导因子1α、心肌营养素1水平较假手术组明显增加(P <0.01),RO492909组两者表达量较模型组均降低;与假手术组比较,模型组小鼠NICD蛋白表达明显增加(P <0.01),RO492909组NICD表达量较模型组降低(P <0.01);与模型组比较,RO492909组小�BACKGROUND: Myocardial ischemia is one of the main causes of cardiac function impairment after myocardial infarction. Notch is involved in the process of angiogenesis, but whether Notch intracellular domain(NICD)/Hes1 is involved in myocardial angiogenesis after myocardial infarction has not been studied.OBJECTIVE: To study the effect of NICD/Hes1 pathway on cardiac function and angiogenesis in the ischemic myocardium of myocardial infarction mice with the aid of RO4929097, a Notch γ secretase inhibitor.METHODS: C57BL/6 mice were randomized into sham, model and RO4929097 groups, with 10 mice in each group. Myocardial infarction model was established in the latter two groups by ligating the left anterior descending coronary artery of C57BL/6 mice. Mice in the RO4929097 group were administered RO4929097 by gavage at the dose of 10 mg/(kg·d) on day 2 after surgery, and those in the sham and model groups were given an equal volume of saline by gavage for 20 days. On day 21, mice were examined by ultrasound for left ventricular ejection fraction, Matson staining for myocardial infarct area and pathohistological changes and immunofluorescence for CD31 in ischemic myocardium. Enzyme-linked immunofluorescence was used to detect the levels of serum vascular endothelial growth factor and basic fibroblast growth factor. Western blot assay was used to detect the expression of hypoxia-inducible factor 1α, cardiotrophin 1, NICD and Hes1 in myocardial tissue.RESULTS AND CONCLUSION: The left ventricular ejection fraction value in the model group was significantly lower than that in the sham group(P < 0.001),while compared with the model group, the left ventricular ejection fraction value was significantly lowered in the RO4929097 group(P < 0.05). Masson staining revealed an significantly increased infarct size in the model group and RO4929097 group compared with the sham group(P < 0.001) as well as an obviously increased infarct size in the RO4929097 group compared with the model group(P < 0.05). The mean absorbance value of

关 键 词：心肌梗死 缺血心肌 血管新生 NICD HES1 

分 类 号：R446[医药卫生—诊断学] R318[医药卫生—临床医学] R496