氨甲酰促红细胞生成素对糖尿病模型大鼠冠脉微循环内皮细胞的影响
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篇名: 氨甲酰促红细胞生成素对糖尿病模型大鼠冠脉微循环内皮细胞的影响
TITLE:
摘要: 目的:研究氨甲酰促红细胞生成素(CEPO)对糖尿病模型大鼠冠脉微循环内皮细胞的影响。方法:取大鼠随机分为空白对照组、模型组和CEPO低、中、高剂量组(500、1 000、2 000 u/kg),每组12只,后4组大鼠建立糖尿病模型;各组大鼠ip相应药物,每周2次,连续4周后分离冠脉微循环内皮细胞。采用酶联免疫吸附法检测各组大鼠外周血清中前列环素(PGI2)、血管收缩因子内皮素1(ET-1)、血管紧张素Ⅱ(AngⅡ)、血管性血友病因子(vWF)的水平;体外CCK8试验检测内皮细胞活力(OD值);实时定量聚合酶链式反应检测内皮细胞中增殖相关基因(Ki67、p16)、凋亡相关基因(Bad、Bax)及血管内皮生长因子(VEGF)和AngⅠ的表达。结果:与空白对照组比较,模型组大鼠外周血清中PGI2、ET-1、AngⅡ、vWF水平均增加,内皮细胞OD值降低,Ki67、p16、Bax、VEGF表达减弱,差异有统计学意义(P<0.05)。与模型组比较,CEPO低、中、高剂量组大鼠外周血清中PGI2、ET-1、AngⅡ、vWF水平均减少,内皮细胞OD值增加,Ki67、p16、VEGF表达增强,Bad、Bax表达减弱,差异有统计学意义(P<0.05);其余差异无统计学意义(P>0.05)。结论:CEPO可能通过上调冠脉微循环内皮细胞VEGF表达,促进冠脉微循环内皮细胞再生,从而改善大鼠糖尿病冠脉微循环功能。
ABSTRACT: OBJECTIVE: To study the effects of carbamylated erythropoietin (CEPO) on cardiovascular microcirculation in rats with diabetes mellitus. METHODS: Rats were randomly divided into blank control group, model group, CEPO low-dose, medium-dose and high-dose groups (500, 1 000, 2 000 u/kg) with 12 in each group. The rats in the last 4 groups were reduced diabetes mellitus model. All rats were given relevant medicine intragastrically twice a week, coronary microcirculation endothelial cells were separated after consecutive 4 weeks. Enzyme-linked immunosorbent assay was conducted to detect levels of peripheral serum prostacyclin (PGI2), vasoconstrictor endothelin-1 (ET-1), angiotensin Ⅱ (AngⅡ) and von Willebrand factor (vWF) of rats in each group; in vitro CCK 8 test was used to detect endothelial cell activity (OD value); real-time quantitative polymerase chain reaction was adopted to detect proliferation-related genes (Ki67, p16), poptosis-related genes (Bad, Bax), and expressions of protein vascular endothelial growth factor (VEGF) and AngⅠ. RESULTS: Compared with blank control group, levels of PGI2, ET-1, AngⅡ and vWF in serum in model group increased; OD value deceased; Ki67, p16, Bax and VEGF expression decreased; the difference was statistically significant (P<0.05). Compared with model group, levels of PGI2, ET-1, AngⅡ and vWF in serum in CEPO low-dose, medium-dose and high-dose groups increased; OD value increased; Ki67, p16 and VEGF expression increased; expressions of Bad and Bax decreased; the difference was statistically significant (P<0.05). The others had no significant difference (P>0.05). CONCLUSIONS: CEPO maybe improve the coronary microcirculation function by upregulating VEGF expression in coronary microcirculation endothelial cells and promoting endothelial cells’ regeneration.
期刊: 2016年第27卷第25期
作者: 黄妍,曾昆,徐彪
AUTHORS: HUANG Yan,ZENG Kun,XU Biao
关键字: 氨甲酰促红细胞生成素;糖尿病;冠脉微循环;内皮细胞;大鼠
KEYWORDS: Carbamylated erythropoietin; Diabetes mellitus; Coronary microcirculation; Endothelial cells; Rat
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