紫檀芪对小鼠缺血性脑损伤的神经保护机制研究

Neuroprotective mechanism of pterostibene on ischemia reperfusion brain injury in mice

目的:探索紫檀芪(PTE)对小鼠缺血性脑损伤中的保护作用及机制。方法:将C57雄性C57BL/6J小鼠分为假手术组(sham)、脑缺血再灌注损伤组(IR)、紫檀芪治疗组(PTE+IR)和紫檀芪阻断剂ZnPP抑制紫檀芪治疗组(PTE+ZnPP+IR),其中PTE的剂量为5 mg/kg,于脑缺血再灌注损伤(IR)前连续5 d每天腹腔给药1次,ZnPP以3 mg/kg的剂量于IR前30 min及IR后24 h分别腹腔给药1次;然后于缺血性脑损伤后0、2、12、24 h及48 h(IR0、IR2、IR12、IR24 h及IR48 h)对小鼠进行神经行为学评分;最后于IR48 h对小鼠进行干湿比重法脑水含量测定,TUNEL试剂盒检测细胞凋亡,Western Blot检测caspase-3及cleaved caspase-3蛋白的表达。结果:PTE可降低缺血性脑损伤后小鼠神经行为学评分、减轻脑水含量、降低细胞凋亡率及下调凋亡蛋白cleaved caspase-3的表达而保护神经细胞,但是PTE的这些神经保护作用可被其抑制剂ZnPP逆转。结论:PTE在鼠脑缺血再灌注损伤中具有明确的保护作用,其机制与减少细胞凋亡有关。

Objective:To explore the protective effects of pterostibene(PTE)on ischemia/reperfusion(IR)brain injury in mice.Methods:The C57BL/6J male mice were randomly divided into four groups:sham group,IR group,PTE+IR group,PTE+IR+ZnPP group.The dose of PTE used was 5 mg/kg once a day for 5 days totally before IR,and the dose of ZnPP used was 3 mg/kg at 30 minutes before IR and 24 h after IR by intraperitoneal injection.The neurological deficit scores were evaluated at 0,2,12,24 h and 48 h after IR(IR0,IR2,IR12,IR24 h and IR48 h),and the brain water content were assessed at 48 h by wet-dried weight after IR.The apoptotic ratio in IR-injured brain were detected by TUNEL staining and the protein expression of caspase-3 and cleaved caspase-3 were detected by Western Blot.Results:PTE improved neurological deficit scores of mice,lowered brain water content and apoptotic ratio,and down-regulated the expression of cleaved casepse-3 after ischemia/reperfusion(IR)injury in mice.However,the neuroprotective effect of PTE was reversed by ZnPP.Conclusion:PTE paly a neuroprotective role against ischemia reperfusion in mice by suppression of cell apoptosis.