摘要
目的:探讨甲状旁腺激素相关肽(PTHrP)的核定位序列(NLS)及C末端共同组成的PTHrP(87-139)片段对小鼠心肌梗死后心脏功能的影响.方法:将C57BL/6野生型雄性小鼠随机分为3组,每组11只.假手术组对心脏前降支穿针但不进行结扎,1d后腹部皮下注射生理盐水;心肌梗死组结扎心脏前降支,1d后腹部皮下注射生理盐水;心肌梗死+PTHrP组结扎心脏前降支,1d后腹部皮下注射PTHrP(87-139),剂量为80μg/kg.各组每日注射1次,持续注射4周后,超声心动图评估心脏功能,免疫组织化学染色检测心肌CD31表达情况,马松染色检测心肌纤维化程度,Western blot检测血管内皮生长因子(VEGF)、血管内皮生长因子受体-2(VEGFR-2)、碱性成纤维细胞生长因子(bFGF)等血管相关因子的表达水平.结果:与假手术组相比,心肌梗死组左室射血分数(LVEF)、左室短轴缩短率(LVFS)均明显降低,左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、心脏质量/体质量比值、肺质量/体质量比值、心肌梗死边缘区的心肌纤维化程度均明显升高(P均<0.05);与心肌梗死组相比,心肌梗死+PTHrP组LVEF、LVFS、LVEDD、LVESD等显著改善,心脏质量/体质量比值、肺质量/体质量比值、心肌梗死边缘区的心肌纤维化程度均明显降低(P均<0.05).与假手术组相比,心肌梗死组心肌梗死边缘区CD31表达水平有轻微升高,但两组间差异无统计学意义,而VEGF、VEGFR-2、bFGF表达水平均明显降低(P均<0.05);与心肌梗死组相比,心肌梗死+PTHrP组CD31、VEGF、VEGFR-2、bFGF表达水平均明显升高(P均<0.05).结论:PTHrP(87-139)能够减少心肌梗死后心肌间质纤维化,促进梗死边缘区新生血管生成,改善心脏功能.
Objective:To investigate the effects of fragment parathyroid hormone-related peptide 87 to 139 [PTHrP(87-139)] consisting of nuclear localization sequence(NLS) and C-terminal fragment of PTHrP on cardiac function after myocardial infarction(MI) in mice. Methods:Male wild-type C57 BL/6 mice were randomly divided into three groups with 11 mice in each group. In the sham-operated group, the anterior descending artery was punctured but not ligated, and the mice were injected subcutaneously at abdomen with normal saline one day later. In the MI group, the anterior descending artery was ligated and normal saline was injected subcutaneously one day later. In the MI+PTHrP group, the anterior descending artery was ligated, and PTHrP(87-139) was injected subcutaneously into the abdomen at a dose of 80 μg/kg one day later. Each group was injected subcutaneously once a day for 4 weeks. Echocardiography was performed to evaluate the cardiac function of mice in each group. Immunohistochemical staining was used to detect the expression of CD31, and the degree of myocardial fibrosis was evaluated by Masson staining. Western blot was used to observe the expression of vascular-related factors such as vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2) and basic fibroblast growth factor(bFGF). Results:Compared with the sham-operated group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening rate(LVFS) significantly decreased, and left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter(LVESD), heart weight/body weight ratio, lung weight/body weight ratio and the degree of myocardial fibrosis in the marginal zone of MI were significantly increased in the MI group(P all<0.05). Compared with the MI group, LVEF, LVFS, LVEDD and LVESD were significantly improved and heart/body weight ratio, lung/body weight ratio and the degree of myocardial fibrosis in the marginal zone of MI were significantly decreased in the MI+PTHrP group(P all<0.05). Compared with the sham-operated group, the expression of CD31 in the marginal zone of MI increased slightly in the MI group, but there was no significant difference between the two groups, while the expression of VEGF, VEGF-2 and bFGF were significantly decreased in the MI group. Compared with the MI group, the expression of CD31, VEGF, VEGFR2 and bFGF in MI+PTHrP group were significantly higher(P all<0.05). Conclusions:PTHrP(87-139) can reduce myocardial interstitial fibrosis after MI, promote angiogenesis at the edge of infarction, and improve cardiac function.
作者
张浩
张定国
夏光伟
王一鸣
高阳
ZHANG Hao;ZHANG Dingguo;XIA Guangwei;WANG Yiming;GAO Yang(Department of Cardiology,The Affiliated Hospital of Yangzhou University,Jiangsu 225000;Department of Cardiology,First Affiliated Hospital of Nanjing Medical University,Jiangsu 210000,China)
出处
《国际心血管病杂志》
2019年第6期336-340,共5页
International Journal of Cardiovascular Disease
基金
国家自然科学基金(81000058)
关键词
心肌梗死
核定位序列
甲状旁腺激素相关肽
Myocardial infarction
Nuclear localization sequence
Parathyroid hormonerelated peptide
