Nobiletin对慢性低灌注损伤后小鼠脑海马神经血管单元的影响

目的观察川陈皮素(NOB)对小鼠慢性脑低灌注(CCH)模型海马区神经血管单元各主要组分的保护作用。方法昆明小鼠随机分为对照组、模型组和NOB高、低剂量处理组各10只,模型组和NOB处理组进行双侧颈总动脉结扎,对照组不结扎。术后2 w进行旷场实验及Y迷宫检测学习记忆功能,Western印迹法测定小鼠海马区神经元生长相关蛋白(GAP)-43、突触素(SYN)、水通道蛋白(AQP)4表达,检测海马神经细胞可塑性及血脑屏障功能。结果与模型组相比,NOB处理组自由活动无显著差异,其中高剂量组探索能力显著增强,逃避潜伏期显著减短(P<0.05);NOB处理组均显著增加海马区GAP-43、SYN、AQP4及Claudin-5表达(P<0.05)。结论NOB可通过对海马的神经血管单元各组分的保护作用,改善CCH所致小鼠学习记忆功能受损。

Effect of Nobiletin on neurovascular unit in mice following chronic cerebral hypoperfusion

Objective To observe the protective effect of Nobiletin(NOB)on the main components of neurovascular units in hippocampal region in chronic cerebral hypoperfusion(CCH)mice.Methods KM mice were randomly divided into control,CCH model,high and low dose NOB groups.Bilateral common carotid artery ligation was performed in CCH model group and NOB groups,and there was no ligation in control group.Two weeks after operation,open field experiment and Y maze were performed to detect the function of learning and memory.Protein expression in hippocampus of neuronal growth associated protein(GAP)-43,synaptophysin(Syn),aquaporin channel(AQP4)and Claudin5 BMECs functional protein were performed by Western blot to detect the neural cell plasticity and blood-brain barrier function.Results Compared with model group,there was no significant difference in free activity in the NOB groups,but exploring ability and escape latency in high dose group were significantly increased(P<0.05).The expression of GAP-43,Syn,AQP4 and Claudin5 in hippocampus were increased both in NOB groups(P<0.05).Conclusions NOB could improve the learning and memory impairment of mice induced by chronic cerebral hypoperfusion through the protective effect of each component of neurovascular unit in hippocampus.