| 王欣,李磊,陈元友,等.柚皮素对心肌梗死大鼠血管新生的促进作用及机制研究[J].浙江中医药大学学报,2021,45(5):441-446, 459. |
| 柚皮素对心肌梗死大鼠血管新生的促进作用及机制研究 |
| Study on the Promoting Effect and Mechanism of Naringenin on Angiogenesis in Rats with Myocardial Infarction |
| DOI：10.16466/j.issn1005-5509.2021.05.002 |
| 中文关键词: 心肌梗死 柚皮素 血管新生 剂量 CD31 MVD VEGF bFGF |
| 英文关键词: myocardial infarction naringenin angiogenesis dosage CD31 MVD VEGF bFGF |
| 基金项目:武汉市卫生和计划生育委员会科研项目(WZ18Q10) |
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| 中文摘要: |
| [目的]观察柚皮素对心肌梗死大鼠血管新生的促进作用及相关机制。[方法]将50只无特定病原体(specific pathogen free，SPF)级SD大鼠随机分为假手术组、模型组、阿司匹林组、柚皮素高剂量组和柚皮素低剂量组，每组10只。采用冠脉动脉前降支结扎法建立大鼠心肌梗死模型，造模第2天开始给药，柚皮素高剂量组和柚皮素低剂量组给予100mg·kg-1和50mg·kg-1柚皮素混悬液灌胃，阿司匹林组予100mg·kg-1阿司匹林水溶液灌胃，假手术组和模型组予0.9%氯化钠溶液20mL·kg-1灌胃，1次/d，连续4周。末次给药结束后检测大鼠心功能指标，苏木素-伊红(hematoxylin-eosin，HE)染色和Masson染色观察心肌组织病理学变化，免疫组化检测心肌组织血小板内皮细胞黏附分子-1(platelet endothelial cell adhesion molecule-1，PECAM-1/CD31)表达，计算微血管密度(microvascular density，MVD)，Western blot检测心肌组织中血管内皮生长因子(vascular endothelial growth factor，VEGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)蛋白表达情况。[结果]与假手术组比较，模型组左室射血分数(left ventricular ejection fractions，LVEF)和左室短轴缩短率(left ventricular factional shortening，LVFS)降低，左室收缩末期内径(left ventricular end-systolic dimension，LVESD)和左室舒张末期内径(left ventricular end-diastolic dimension，LVEDD)增加；与模型组比较，阿司匹林组、柚皮素高剂量组和柚皮素低剂量组LVEF和LVFS增加，LVESD和LVEDD降低。HE染色和Masson染色结果显示，与假手术组比较，模型组大鼠心肌组织排列紊乱，纤维化明显；与模型组比较，柚皮素高剂量组心肌组织排列较为整齐，胶原纤维沉积减少，但柚皮素低剂量组心肌组织分布相对较紊乱，仍有明显胶原纤维沉积。免疫组化检测结果显示，模型组CD31表达水平和MVD高于假手术组；与模型组比较，柚皮素高剂量组和柚皮素低剂量组CD31表达水平和MVD增加，其中柚皮素高剂量组CD31表达水平和MVD高于阿司匹林组和柚皮素低剂量组。Western blot检测结果显示，与假手术组比较，模型组VEGF、bFGF蛋白表达水平增加；与模型组比较，阿司匹林组、柚皮素高剂量组和柚皮素低剂量组VEGF、bFGF蛋白表达水平增加，其中柚皮素高剂量组VEGF、bFGF蛋白表达水平高于阿司匹林组和柚皮素低剂量组。上述指标差异均有统计学意义(P＜0.05)。[结论]柚皮素能够促进心肌梗死大鼠血管新生，其作用机制可能与促进VEGF、bFGF蛋白表达有关。 |
| 英文摘要: |
| [Objective] To observe the effect of naringenin on angiogenesis in rats with myocardial infarction and related mechanism.[Methods]Fifty specific pathogen free(SPF) SD rats were randomly divided into sham operation group， model group， aspirin group， naringenin high-dose group and naringenin low-dose group， with 10 rats in each group. Myocardial infarction model was established by ligation of anterior descending branch of coronary artery in rats. On the second day of modeling， naringenin high-dose group and naringenin low-dose group were given naringenin suspension 100mg·kg-1 and 50mg·kg-1 by gavage， aspirin group was given 100mg·kg-1 aspirin enteric coated tablets， sham operation group and model group were given 20mL·kg-1 0.9% sodium chloride solution， once a day for 4 weeks. At the end of the last administration， cardiac function indexes were detected. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes of myocardial tissues. Immunohistochemical staining was used to detect the expression of platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)， and microvascular density(MVD) was calculated. Western blot was used to detect the protein expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in myocardial tissues.[Results] Compared with sham operation group， left ventricular ejection fractions(LVEF) and left ventricular factional shortening(LVFS) were decreased， left ventricular end-systolic dimension(LVESD) and left ventricular end-diastolic dimension(LVEDD) were increased in model group. Compared with model group， LVEF and LVFS were increased in aspirin group， naringenin high-dose group and naringenin low-dose group， while LVESD and LVEDD were decreased. The results of HE staining and Masson staining showed that compared with sham operation group， the myocardial tissue arrangement of model group was disordered and the fibrosis was obvious. Compared with model group， the myocardial tissue in the naringenin high-dose group was more orderly， and the collagen fiber deposition was reduced， but the myocardial tissue distribution in the naringenin low-dose group was relatively disordered， and there was still obvious collagen fiber deposition. The results of immunohistochemistry showed that the expression level of CD31 and the MVD in model group were higher than those in sham operation group. Compared with model group， the expression level of CD31 and the MVD in naringenin high-dose group and naringenin low-dose group increased. Among them， the expression level of CD31 and the MVD in naringenin high-dose group were higher than those in aspirin group and naringenin low-dose group. Western blot results showed that compared with sham operation group， the expression levels of VEGF and bFGF protein in model group increased. Compared with model group， the expression levels of VEGF and bFGF protein increased in aspirin group， naringenin high-dose group and naringenin low-dose group. Among them， the VEGF and bFGF protein expression levels in naringenin high-dose group were higher than those in aspirin group and naringenin low-dose group. The differences in the above indicators were statistically significant(P＜0.05).[Conclusion]Naringenin can promote angiogenesis in rats with myocardial infarction， and its mechanism may be related to promotion of the protein expression of VEGF and bFGF. |
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