目的:探究小檗碱对慢性低灌注脑损伤小鼠神经保护作用的机制。方法:采用单侧颈总动脉永久性结扎(Unilateral Common Carotid Artery Occlusion UCCAO)方法建立慢性脑低灌注小鼠模型，随机分为5组(n=10)，分别为假手术组、模型组、按小檗碱剂量不同分为低剂量组、中剂量组和高剂量组，连续灌胃给药21天。采用走平横木实验和Morris水迷宫评定小鼠精细运动能力和学习记忆能力。采用E1ISA方法检测小鼠海马和皮质的炎症指标IL-1β、NLRP3和TNF-α。结果:与模型组比较，小檗碱中剂量和小檗碱高剂量组精细运动能力明显提高(P＜0。01)，小檗碱低剂量无显著性变化(P＞0。05)。与模型组比较，小檗碱中剂量和小檗碱高剂量组认知能力明显提高(P＜0。01)，小檗碱低剂量无显著性变化(P＞0。05)。与模型组比较，小檗碱中剂量和小檗碱高剂量组小鼠海马区和皮质区TNF-a、IL-1β、NLRP3的表达显著减少，小檗碱低剂量组IL-1β无显著性变化(P＞0。05)。结论:小檗碱可提高慢性低灌注脑损伤小鼠的精细运动能力并对其认知功能障碍具有改善作用，同时减少神经炎症反应，具有神经保护作用。
Neuroprotective Effect of Berberine on Chronic Hypoperfusion Brain Injury in Mice
Objective:To investigate the neuroprotective mechanism of berberine on chronic hypoperfusion brain injury in mice.Methods:Unilateral common carotid artery occlusion(UCCAO)was used to establish chronic cerebral hypoperfusion model in mice.The mice were randomly divided into 6 groups(n=10):sham operation group,model group,According to the different doses of berber-ine,they were divided into low-dose group,medium-dose group and high-dose group,intragastric administration for 21 days.The fine motor ability and learning memory ability of mice were evaluated by horizontal crossbar test and Morris water maze.IL-1 β,NLRP3 and TNF-α were detected by ELISA.Results:Compared with the model group,the fine motor ability of middle dose and high dose berberine groups was significantly improved(P＜0.01),while low dose berberine had no significant change(P＜0.05).Compared with model group,cognitive ability of middle dose and high dose berberine groups was significantly improved(P＜0.01),while low dose berberine had no significant change(P＜0.05).Compared with the model group,the expression of TNF-α,IL-1β,NLRP3 in hippocampus and cortex of mice in middle and high dose berberine groups decreased significantly,significantly,while low dose berberine IL-1 β of berberine had no significant change(P＜0.05).Conclusion:Berberine can improve the fine motor ability and cognitive dysfunction of mice with chronic hypoperfusion brain injury,and reduce neuroinflammatory reaction,which has neuroprotective effect.
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