依达拉奉对急性脑缺血/再灌注大鼠AQP4和Aβ表达及MMP-2和MMP-9活性的影响

Effect of edaravone on expression of Aβ and AQP4 and activity of MMP2 and MMP9 in acute cerebral ischemia/reperfusion rats

目的:探讨依达拉奉对急性脑缺血/再灌注大鼠脑损伤的治疗效果及其作用机制。方法:选取健康雄性SPF级SD大鼠,采用随机数字表法分为假手术组(等体积生理盐水)、模型组(造模后给予等体积生理盐水)、低剂量组(依达拉奉6 mg/kg)和高剂量组(依达拉奉10 mg/kg),采用Zea Longa线栓法造模,并对各组大鼠在术后的神经功能评分,TTC法测定脑梗死体积;采用RT-qPCR法检测脑组织中水通道蛋白4(aquaporin 4,AQP4)和β-淀粉样蛋白(amyloidβ-protein,Aβ)的mRNA表达; Western blot法检测Aβ及AQP4的蛋白水平;采用明胶酶谱法检测基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)和MMP9的活性。结果:相对于模型组,依达拉奉能显著减轻大鼠神经功能障碍、组织学损伤和脑水肿,降低AQP4和AβmRNA和蛋白水平及MMP2和MMP9活性,且高剂量组效果优于低剂量组(P <0. 05)。结论:依达拉奉减轻急性缺血性脑卒中大鼠脑组织损伤的机制可能与其抑制AQP4和Aβ表达及MMP2和MMP9活性有关。

AIM:To investigate the effect of edaravone on acute cerebral ischemia/reperfusion rats.METHODS:SD rats were randomly divided into sham operation group(saline),model group(modeling given saline),low dose group(edaravone at 6 mg/kg)and high dose group(edaravone at 10 mg/kg).The rat model was established by Zea Longa suture method.The nerve function scores were evaluated after operation,and the infarct volume was measured by TTC assay.The mRNA expression of aquaporin 4(AQP4)and amyloidβ-protein(Aβ)in the brain tissue was detected by RT-qPCR.The protein levels of APQ4 and Aβwere determined by Western blot.The activity of matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9)was detected by gelatin zymography.RESULTS:Compared with model group,edaravone administration markedly alleviated neurological deficits,histological damages and brain edema.The mRNA and protein levels of AQP4 and Aβ,and the activity of MMP2 and MMP9 were downregulated(P<0.05).Furthermore,the improvements in high dose group were significantly more effective than those in low dose group.CONCLUSION:Edaravone significantly reduces neurological deficits and brain edema in the rats with acute ischemic stroke,and the mechanisms may be related to the downregulation of AQP4 and Aβ,and the activation of MMP2 and MMP9.