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NO与AngII的调节对大鼠心肌缺血的作用及VEGF表达的影响 被引量:1

Regulatory Effects of Nitric Oxide and Angiotensin II on Myocardial Ischemia and Expression of Vascular Endothelial Growth Factor in Rats
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摘要 目的:探讨氧化亚氮(NO)与血管紧张素II(Ang II)的调节对大鼠心肌缺血的作用及血管内皮生长因子(VEGF)表达的影响。方法:将30只SD大鼠随机分成5组(每组均为6只):A:对照组(COL)、B:异丙肾上腺素组(ISO)、C:异丙肾上腺素+氯沙坦组(LOS)、D:异丙肾上腺素+硝基左旋精氨酸组(L-NNA)、E:异丙肾上腺素+氯沙坦+硝基左旋精氨酸组(LOS+L-NNA)。由异丙肾上腺素(ISO)诱导大鼠心肌缺血模型;选用硝基左旋精氨酸(L-NNA)阻断氧化亚氮合酶(NOS),氯沙坦(LOS)阻断Ang II选择性受体AT1;BL-420F生物信号处理系统监测心功能指标;生物化学方法检测心肌NO、血清肌酸激酶(CK),HE染色观察心肌细胞损伤情况,免疫组化染色分析VEGF及eNOS的蛋白表达,RT-PCR半定量检测VEGF、eNOS在心肌中mRNA表达。结果:C组心功能与B、D、E组相比得到明显改善(P<0.01),心肌细胞损伤明显减轻;C组NO释放量与B、D、E组相比明显升高(P<0.01);C组心肌VEGF mRNA及蛋白表达与其他各组相比均增加(P<0.01);C和E组eNOS mRNA和蛋白表达与B和D组相比明显增加(P<0.01)。结论:阻断AT1受体可上调大鼠心肌VEGF的表达,大鼠心肌缺血过程中NO和AngII-AT1受体信号转导通路对VEGF表达起重要调节作用。氯沙坦可部分通过对心肌eNOS、VEGF的表达以及NO的调节对心肌有保护作用。 Objective:To investigate the regulatory effects of nitric oxide (NO) and angiotensin Ⅱ (Ang Ⅱ) on myocardial ischemia and the expression of vascular endothelial growth factor in rats. Methods: Thirty Sprague-Dawley rats were randomized into five groups (n = 6 each), including the control group (COL, group A), the isoproterenol group (ISO, group B), the isoproterenol + losartan group (LOS, group C ), the isoproterenol + N-nitro-L-arginine group (L-NNA, group D)and the isoproterenol + losartan + N-nitro-L-arginine group (LOS+ L-NNA, group E). Acute myocardial ischemia model was induced with isoproterenol ( ISO ). N-nitro-L-arginine ( L-NNA ) was used to block the nitric oxide synthase (NOS) , as was losartan (LOS) to block the AT1 receptor. Cardiac function was measured with a BL-420 biological signal processing system, contents of NO and creatine kinase (CK) measured by biochemistry methods, myocardial injury studied by HE stained histopatholagy, and expressions of VEGF and endothelial nitric oxide synthase (eNOS) analyzed by immunohistochemistry. RT-PCR was employed to detect the VEGF mRNA and eNOS mRNA in myocardium. Results: Compared with groups B, D and E, group C showed improved cardiac functions, attenuated myocardial damages (P 〈 0.01 ) and increased content of nitric oxide (P 〈 0. 01 ). Enhanced expressions of VEGF mRNA and protein were also noted in C group compared with the other groups (P 〈0.01 ). The levels of eNOS mRNA and protein expression were higher in groups C and E than in groups C and D (P 〈 0. 01 ). Conclusion: Blockade of Ang Ⅱ type 1 receptor was shown to up-regulate VEGF expression in rat myocardium. Nitric oxide and angiotensin Ⅱ type 1 receptor signaling pathway may be playing a critical role in regulating VEGF expression. Losartan appeared protective for myocardium partly due to its regulation on VEGF and eNOS expressions and nitric oxide activity.
出处 《广州医学院学报》 2007年第5期1-6,共6页 Academic Journal of Guangzhou Medical College
关键词 心肌缺血 血管内皮生长因子 氧化亚氮 血管紧张素Ⅱ 大鼠 myocardial ischemia vascular endothelial growth factor nitric oxide angiotensin Ⅱ rat
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参考文献10

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