Protective effects of 3-n-butylphthalide on the cognitive dysfunction of chronic cerebral ischemic rats and its biochemical mechanisms / 中华老年医学杂志

ABSTRACT

Objective To investigate the protective effects of 3-n-butylphthalide (dl-NBP) on the cognitive dysfunction of chronic cerebral ischemic rats and its mechanism.Methods Old chronic cerebral ischemic rats (15 months) were modelized with ligating bilateral common carotid arteries for three months.Model rats were divided into four groupssham,model,NBP 30 and 120 mg · kg-1 groups.The former and the latter two groups were administered vegetable oil and NBP for 45 days,respectively.Then,the cognitive function was measured in rats with Morris water maze.Meanwhile,the activities of superoxide dismutase (SOD),choline acetyltransferase (ChAT),true choline esterase (TChE),and the malondialdehyde (MDA) levels in brain cortex and hippocampus were detected with biochemical methods.Results During the five days of Morris water maze,the change of escape latency was from (57.7±3.8) s to (30.5±17.1) s in low dose of NBP group,and from (58.4±1.8) s to (28.9±11.3) s in high dose of NBP group as compared with no change from 60s to 60s in model group.Significant differences were found in escape latency between NBP's and model groups(P＜0.05 or 0.01).In spatial exploratory test,the time percentages spent in the platformquadrant were increased obviously in low and high doses of NBP [(26.0±6.9) ％ and (27.3±5.3) ％,respectively,P＜0.05],compared with that of model group.The SOD activity was obviously reduced in cortices of high dose of NBP group [(112.3 ± 7.6) U/mg protein] compared with that (134.6 ± 13.9) U/mg protein of model group (P＜0.01).The MDA contents were significantly reduced in cortices of low and high doses of NBP (2.39±0.31) nmol/mg protein and (1.56±0.19) nmol/mg protein,compared with that of model group (P＜0.01).The MDA contents in hippocampi of low and high doses of NBP [(0.71±0.10) nmol/mg protein and (0.83±0.05) nmol/mg protein] were also decreased significantly,compared with that of model group (P＜0.01).The ChAT level in cortex of high dose of NBP was increased significantly [(1615 ± 100) U/g protein,P＜0.05].The ChAT level in hippocampi of two doses of NBP also increased significantly [(1746±204) U/g protein and (1697± 117) U/g protein,P＜0.05].Conclusions NBP may improve cognition damage of chronic cerebral ischemic rats by ameliorating oxidative stress lesion and enhancing the activity of cholinergic nerve in brain tissue.