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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 effects of nitric oxide (NO) and angiotensin II (Ang II) on myocardial ischemia and the expression of vascular endothelial growth factor (VEGF) in rats. METHODS: Thirty SD rats were randomly divided into 5 groups (6 in each group): A: control group (COL), B: isoproterenol group (ISO), C: isoproterenol + losartan (LOS), D: isoprenaline + L-arginine group (L-NNA), E: isoprenaline + losartan + L-arginine group . Myocardial ischemia model was induced by isoproterenol (ISO). L-NNA was used to block nitric oxide synthase (NOS) and Losartan (LOS) The expression of VEGF and eNOS protein were detected by immunohistochemical staining. The expression of VEGF and eNOS protein were detected by immunohistochemical staining. RT-PCR semi-quantitative detection of VEGF, eNOS mRNA expression in the myocardium. Results: The cardiac function in group C was significantly improved compared with that in groups B, D and E (P <0.01), and the myocardial injury was significantly reduced. The NO release in group C was significantly higher than that in groups B, D and E (P < 0.01). The expression of VEGF mRNA and protein in myocardium of group C were increased compared with other groups (P <0.01). The expression of eNOS mRNA and protein in group C and E were significantly increased compared with group B and D (P <0.01). CONCLUSION: Blocking AT1 receptor can up-regulate the expression of VEGF in rat myocardium. NO and AngII-AT1 receptor signal transduction pathways play an important role in the regulation of VEGF expression during myocardial ischemia in rats. Losartan may have protective effect on myocardium partly through the expression of eNOS, VEGF and NO in myocardium.