葛根素治疗急性脊髓缺血再灌注损伤大鼠的神经保护机制

The Mechanism of Neuroprotective Effects of Puerarin for the Treatment of Acute Spinal Ischemia-reperfusion Injury in Rats

目的探索葛根素在治疗急性脊髓缺血再灌注损伤(ASII)大鼠中的作用机制。方法 28只雄性大鼠阻断主动脉来实施ASII。实验动物随机分为4组:阴性对照(NC)组(假手术处理)、阳性对照(IR+S)组(脊髓缺血再灌注损伤+盐水处理)、IR+P组(脊髓缺血再灌注损伤+葛根素处理)、IR+R组(脊髓缺血再灌注损伤+细胞周期蛋白B激酶抑制剂处理)。检测各组大鼠运动机能、脊髓梗死体积、细胞凋亡指数及细胞周期素依赖性激酶5(CDK5)和P25的活性。结果 IR+S组与NC组比较,P35和P25蛋白表达差异有统计学意义(P<0.01);IR+P组、IR+R组与IR+S组比较差异亦有统计学意义(P<0.05)。提示葛根素对ASII神经保护可能通过类似抑制剂的作用,并且与P35和P25的表达相关。结论脊髓损伤减小与CDK5及P25活性受抑制相关;在ASII大鼠治疗过程中,抑制CDK5及P25活性是葛根素的神经保护机制之一。

Objective To explore the mechanism of neuroprotective effects of puerarin for the treatment of acute spinal ischemia-reperfusion injury in a rat model. Methods Acute spinal ischemia-reperfusion injury was induced via aortic occlusion in 28 male Sprague-Dawley rats.The animals were randomly divided into four groups,as follows：group negative contrast（NC sham operation）,group positive control group（IR＋S ischemia/reperfusion ＋ saline）,group puerarin（IR＋P ischemia/reperfusion ＋ puerarin）,group roscovitine（IR＋R ischemia/reperfusion ＋ roscovitine）.The motor function,spinal infarction volume,apoptosis indices,and CDK5 and P25 activities were examined. Results Spinal ischemia-reperfusion caused the injury of the spines and was associated with motor deficit,elevation of CDK5 and P25 activities,and increase in the spinal apoptosis and spinal infarction volume. Puerarin improved motor function and decreased apoptosis,spinal infarction volume,and CDK5 and P25 activities. Conclusion The findings of the present study indicated that puerarin treatment-mediated reduction of spinal injury was associated with the inhibition of CDK5 and P25,and that the inhibition was one among the neuroprotective mechanisms of puerarin against acute ischemia/reperfusioninduced spinal injury in rats.