利拉鲁肽对急性心肌梗死大鼠血管新生和心肌保护的影响及机制研究
本文选题:心肌梗死 + 血管新生 ; 参考:《中国循环杂志》2017年11期
【摘要】:目的:观察利拉鲁肽对急性心肌梗死大鼠心肌血管新生的影响及其心肌保护作用。方法:冠状动脉结扎法建立大鼠急性心肌梗死模型,成功建模的大鼠随机分为三组(每组6只):对照组、利拉鲁肽低剂量组(LS组)和利拉鲁肽高剂量组(HS组),另外取6只大鼠仅穿线,不结扎,作为假手术组。LS组和HS组建模后分别腹腔皮下注射利拉鲁肽70μg/(kg·d)和140μg/(kg·d),假手术组和对照组均注射相应生理盐水,每天1次,共2周。4周后,超声心动图评估大鼠心脏结构及功能,HE染色观察心肌组织形态学变化,Masson染色计算胶原容积分数(CVF),免疫组织化学法检测大鼠心肌梗死边缘区微血管密度(MVD)及血管内皮生长因子(VEGF)蛋白表达,蛋白免疫印迹(Western blot)法检测VEGF蛋白含量。结果:4周后,对照组较假手术组左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)均明显减低,左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)及CVF明显增加(P均0.01),而MVD及VEGF蛋白水平差异无统计学意义(P0.05);与对照组相比,LS组和HS组LVEF、LVFS明显升高(P0.01),LVEDd、LVESd降低(P0.05),CVF明显下降(P0.01),MVD及VEGF蛋白水平显著增加(P0.01);HS组较LS组LVEF、LVFS明显升高(P0.01),LVEDd、LVESd和CVF下降(P0.05),MVD及VEGF蛋白水平增加(P0.01或P0.05)。结论:利拉鲁肽可促进急性心肌梗死大鼠血管新生,可能与增加VEGF蛋白表达有关,并可减少胶原沉积,从而改善左心室收缩功能,发挥心肌保护作用,且与剂量有一定关系。
[Abstract]:Aim: to observe the effect of liralutin on myocardial angiogenesis and myocardial protection in rats with acute myocardial infarction (AMI). Methods: rat models of acute myocardial infarction were established by coronary artery ligation. The rats were randomly divided into three groups (6 rats in each group: control group). The low dose group (LS group) and the high dose group (HS group) were selected. The other 6 rats were taken out without ligation. After modeling as sham-operation group, LS group and HS group, respectively, 70 渭 g/(kg d and 140 渭 g/(kg d of liraropeptide were injected subcutaneously into the abdominal cavity. The sham operation group and control group were injected with corresponding saline once a day for 2 weeks, 4 weeks later. Evaluation of Cardiac structure and function by Echocardiography in Rats the changes of myocardial histomorphology were observed by Masson staining and collagen volume fraction (CVFN) was calculated by Masson staining. Microvessel density (MVD) and intravascular density (MVD) were detected by immunohistochemical method in the marginal area of myocardial infarction in rats. The expression of skin growth factor (VEGF) protein, The content of VEGF protein was detected by Western blotting. Results after 4 weeks, the left ventricular ejection fraction (LVEF) and the left ventricular shortening rate (LVFS) in the control group were significantly lower than those in the sham-operated group. Left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVESd) and CVF increased significantly (P 0.01), but there was no significant difference in MVD and VEGF protein levels between LS group and HS group (P 0.05). The levels of MVD and VEGF protein were significantly increased in HS group than those in LS group. Compared with LS group, the levels of LVEDd and CVF in HS group were significantly higher than those in LS group. The levels of MVD and VEGF protein in HS group were significantly higher than those in LS group (P 0.01 or P 0.05). Conclusion: Lilaru peptide can promote angiogenesis in rats with acute myocardial infarction, which may be related to the increase of VEGF protein expression, decrease collagen deposition, improve left ventricular systolic function and exert myocardial protection.
【作者单位】: 中山大学附属第五医院心血管内科;中山大学附属第五医院放射科;中山大学附属第五医院超声科;
【分类号】:R-332;R542.22
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