Rac1 对糖尿病大鼠脑缺血后血管新生的影响机制的研究

目的:通过观察糖尿病大鼠脑缺血后,脑组织内Rac1表达的变化及其对VEGF、SDF-1表达的影响,探讨不同血糖水平时Rac1对脑缺血后血管新生的影响机制。方法:腹腔注射链脲霉素制作糖尿病大鼠脑缺血模型,尾静脉注射Rac1抑制剂NSC23766,通过western blotting法检测脑组织中总Rac1、VEGF和SDF-1表达;通过GST-pulldown法检测脑组织中活性Rac1表达。结果:在糖尿病大鼠脑缺血模型中,VEGF和SDF-1的表达随着血糖水平的升高而下降;脑组织内Rac1蛋白表达随着血糖水平升高而减少;抑制Rac1活性后,脑组织中VEGF表达均下降但SDF-1的表达反而增加。结论:在糖尿病大鼠脑缺血模型中,高血糖可抑制脑组织Rac1、VEGF和SDF-1的水平,该抑制作用随着血糖升高而增加。抑制Rac1水平可抑制VEGF表达但并未抑制SDF-1水平,提示高血糖可能通过抑制Rac1导致VEGF表达下降,从而影响血管新生。

The Influence of Rac1 in the Angiogenesis of Diabetic Rats after Cerebral Ischemia

Objective:Through the observation of the expression changes of Rac1 in brain tissue and its effect on the expression of SDF-1, VEGF, study the influence mechanism of Rac1 on angiogenesis after cerebral ischemia in diabetic rats.Methods:For diabetic rat model of focal cerebral ischemia, streptozotocin was administed to the rats by intraperitoneal injection, Rac1 inhibitor NSC23766 was given in diabetic model rats by tail intravenous injection. The expression levels of total Rac1, VEGF and SDF-1 were examined by western blotting method. The expression of activated Rac1 was examined by GST-pulldown technology.Results:In ischemia model of diabetic rat, the expression levels of VEGF and SDF-1 decreased with increasing blood glucose levels; the expression level of Rac1 decreased with elevated blood glucose levels in brain tissue. When the activation of Rac1 was inhibited, the expression level of VEGF was reduced, but expression level of SDF-1 was increased.Conclusion:In ischemia model of diabetic rat, hyperglycemia can inhibit the expression levels of Rac1, VEGF and SDF-1 in brain tissue, and the inhibition increased with the increase of blood glucose. The inhibition of Rac1 can inhibit VEGF expression but did not inhibit the expression level of SDF-1, suggesting that high glucose may inhibit Rac1 resulted in decreased VEGF expression, thus affecting angiogenesis.