bpV（pic）对血管性痴呆模型大鼠行为学及海马p-PKB(Ser473)表达的影响

Effect of bpV（pic） on behavior and the level of p-PKB(Ser473) of hippocampal neurons in vascular dementia model rats

目的:探讨钒氧化合物[双过氧二钾(吡啶-2-羧基)氧代钒酸盐,bpV(pic)]对血管性痴呆(VD)模型大鼠认知功能和海马神经元凋亡的作用及机制。方法:将36只SD成年雄鼠分为4组:sham组、sham+bpV(pic)组、VD组及VD+bpV(pic)组。VD+bpV(pic)组大鼠造模后,bpV(pic)(1 mg/kg,10 ml)连续灌胃21 d,用Morris水迷宫(MWM)检测动物认知功能变化,用HE染色检测动物海马组织神经元病理形态学变化,用Wesern blot检测神经元天冬氨酸特异性半胱氨酸蛋白酶3剪切体(cleaved-caspase-3)和第473位丝氨酸磷酸化蛋白激酶B[p-PKB(Ser 473)]水平变化。结果:与VD模型组比较,VD+bpV(pic)组动物空间学习记忆功能缺陷改善(P<0.05);海马神经元的形态学损伤减轻;神经元cleaved-caspase-3表达降低(P<0.05);神经元p-PKB(Ser 473)水平升高(P<0.05)。结论:bpV(pic)可通过激活蛋白激酶B(PKB)活性来降低VD模型大鼠的空间学习记忆功能缺损和减少海马神经元凋亡。

Objective To explore the effect and mechanism of dipotassium bisperoxo(pyridine-2-carboxyl)oxovanadate[bpV(pic)]on cognitive function and apoptosis of hippocampal neurons in vascular dementia(VD)model rats.Methods Thirty-six adult male SD rats were divided into four groups:Sham group,Sham+bpV(pic)group,VD group and VD+bpV(pic)group.After the establishment of vascular dementia model,the VD+bpV(pic)group rats were given intragastric administration of bpV(pic)(1 mg/kg,10 ml)for 21 consecutive days.The changes of cognitive function were detected by Morris water maze(MWM).After finishing the behavior tests,the morphological changes of hippocampal neurons were detected by HE staining,and the levels of cleaved-caspase-3 and phosphorylated protein kinase B on Ser 473[p-PKB(Ser 473)]were detected by Western blot.Results Compared with VD group,VD+bpV(pic)improved the spatial learning and memory deficit(P<0.05),reduced the morphological damage of hippocampal neurons,reduced the expression of cleaved-caspase-3 in neurons(P<0.05),and increased the level of p-PKB(Ser 473)in neurons(P<0.05).Conclusion BpV(pic)can reduce spatial learning and memory deficits and neuronal apoptosis in hippocampus of VD model rats by enhancing protein kinase B activity.