亚低温对脑缺血再灌注大鼠血管内皮生长因子和低氧诱导因子-1α表达的影响

Effect of Mild Hypothermia on Expression of Vascular Endothelial Growth Factor and Hypoxia-inducible Factor-1α in Rats with Cerebral Ischemia-reperfusion

目的探讨亚低温对脑缺血再灌注大鼠内皮生长因子(VEGF)和低氧诱导因子-1α(HIF-1α)表达的影响。方法 30只Sprague-Dawley大鼠随机分为假手术组、模型组和亚低温组,每组10只。后两组制备大脑中动脉闭塞(MCAO)2 h再灌注动物模型,亚低温组进行亚低温处理24 h。Longa评分评估各组大鼠神经功能;湿/干重法测定脑含水量;TTC染色观察脑梗死体积;ELISA法检测脑组织VEGF、HIF-1α蛋白含量;q PCR法检测脑组织VEGF m RNA水平。结果与假手术组比,模型组神经行为学评分升高,脑含水量及脑梗死率增加,脑组织HIF-1α蛋白、VEGF蛋白及m RNA水平上调(P<0.05)。与模型组比,亚低温组神经神经行为学评分显著降低(χ~2=26.657,P<0.001),脑含水量及脑梗死率降低,脑组织HIF-1α蛋白、VEGF蛋白及m RNA水平进一步上调(P<0.05)。结论亚低温可能通过HIF-1α介导VEGF上调,促进缺血组织区新生血管形成,从而发挥对缺血性脑卒中的保护作用。

Objective To observe the effect of mild hypothermia on expression of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） in brain tissues in rats with cerebral ischemia-reperfusion, Methods Thirty Sprague-Dawley rats were randomly divided into sham group, model group and mild hypothermia group with ten rats in each group. The latter two groups were established middle cerebral artery occlusion （MCAO） for two hours and reperfusion model. The mild hypothermia group received mild hypothermia treatment for 24 hours. The neurologic function was evaluated with Longa＇s score. The brain water content was measured by wet/dry method. The infarction area ratio was assessed by TTC staining. The protein levels of VEGF and HIF-1α were determined by ELISA, while the mRNA level of VEGF was assessed by qPCR. Results Compared with the sham group, the score of neurologic score, the brain water content ratio and the infarction area ratio, the expression of VEGF protein and HIF-1α protein, and the mRNA level of VEGF increased in the model group （P〈0.05）. Compared with the model group, the score ofneurologic score significantly decreased （X^2=26.657, P〈0.001）, the brain water content ratio and the infarction area ratio decreased （P〈0.05）, and the expression of VEGF protein and HIF-1α protein, and the rnRNA level of VEGF further increased （P〈0.05） in the mild hypothermia group. Conclusion Mild hypothermia may protect against ischemic-induced neurologic injury by up-regulating the expression of VEGF and HIF-1α, and promote the angiogenesis in the rats with cerebral ischemia-reperfusion.