红景天对急性心肌梗死大鼠心肌组织Ⅷ因子相关抗原、低氧诱导因子和血管内皮生长因子表达的影响(英文)

Effects of Radix et Rhizoma Rhodiolae Kirilowii on expressions of von Willebrand factor,hypoxia-inducible factor 1 and vascular endothelial growth factor in myocardium of rats with acute myocardial infarction

目的:观察红景天对急性心肌梗死(acute myocardial infarction,AMI)大鼠心肌组织低氧诱导因子1α(hypoxia-inducible factor1α,HIF-1α)、低氧诱导因子1β(hypoxia-inducible factor1β,HIF-1β)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响,探讨红景天促进大鼠缺血心肌血管新生的机制,并了解红景天苷是否为红景天发挥这些作用的有效成分。方法:建立Wistar大鼠AMI模型,造模前7d开始分组灌胃生理盐水(对照组)、红景天(红景天组)或红景天苷(红景天苷组),每组12只。灌胃持续至造模手术后第7天,处死动物取心脏标本。免疫组织化学方法检测梗死心肌边缘区和非梗死区Ⅷ因子相关抗原(von Willebrand factor,v WF)的表达,计算其免疫组织化学指数;实时定量聚合酶链式反应(polymerase chain reaction,PCR)方法检测心肌组织HIF-1α、HIF-1β、VEGF mRNA的表达;蛋白印迹方法检测HIF-1α、HIF-1β、VEGF蛋白的表达。结果:红景天组梗死边缘区和非梗死区心肌v WF蛋白表达均显著高于对照组(P<0.05);红景天组HIF-1α、HIF-1β、VEGF mRNA表达和HIF-1α、VEGF蛋白表达均较对照组显著升高(P<0.01),HIF-1β蛋白水平虽较对照组升高,但差异无统计学意义(P>0.05)。红景天苷组各指标的表达水平均介于对照组和红景天组之间。结论:红景天具有促进AMI大鼠心肌血管新生的作用,其机制可能与上调HIF-1α、HIF-1β、VEGF表达有关。红景天苷可能是红景天发挥上述作用的有效成分之一。

Objective： To investigate the effects of Radix et Rhizoma Rhodiolae Kirilowii on angiogenesis and expressions of hypoxia-inducible factor 1α （HIF-1α）, hypoxia-inducible factor 1β （HIF-1β） and vascular endothelial growth factor （VEGF） in myocardium of rats with acute myocardial infarction （AMI）, to elucidate the possible mechanism of Radix et Rhizoma Rhodiolae Kirilowii in promoting angiogenesis, and to investigate that whether or not salidroside could be considered as the effective component of Radix et Rhizoma Rhodiolae Kirilowii with regard to the effects mentioned above. Methods： Thirty-six male Wistar rats had the anterior descending branch of coronary artery ligated as AMI model. Rats were fed with normal saline （untreated group）, Radix et Rhizoma Rhodiolae Kirilowii solution （Radix et Rhizoma Rhodiolae Kirilowii group） or salidroside solution （salidroside group） from 7 days before until 7 days after the operation, with twelve rats in each group. All rats were sacrificed 7 days after the operation. Immunohistochemical assay （IHC） was used for detecting the expression of von Willebrand factor （vWF） ; TaqMan real-time quantitative polymerase chain reaction （PCR） assay was employed for detection of the levels of HIF-1α, HIF-1β and VEGF mRNAs; Western blot analysis was used for detection of the corresponding protein levels. Results： Results of IHC index showed that both at infarct border zone and non-infarct zone, the expressions of vWF were significantly increased in Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group （P〈0. 05）. The expressions of HIF-1α, HIF-1β and VEGF mRNAs and the expressions of HIF- 1α and VEGF proteins were significantly increased in the Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group （ P〈0.01）. The level of HIF-1β protein in the Radix et Rhizoma Rhodiolae Kirilowii group was also higher than that in the untreated group but the difference was not statistically significant （P〉0.05）. All the expression levels, including those of vWF, HIF-1α, HIF-1β and VEGF, in the salidroside group were higher than those in the untreated group while lower than those in the Radix et Rhizoma Rhodiolae Kirilowii group. Conclusion： Radix et Rhizoma Rhodiolae Kirilowii may promote angiogenesis in myocardium of rats with AMI through elevating the expressions of HIF-1α, HIF-1β, and VEGF. Salidroside may be one of the effective components in Radix et Rhizoma Rhodiolae Kirilowii, which increases the expressions of HIF-1α, HIF-1β and VEGF during ischemia or hypoxia.