CAJ | 학술논문

目的观察消旋丁苯酞(dl-NBP)对慢性脑缺血大鼠认知的改善作用,并研究其生化机制. 方法永久性结扎老龄大鼠(15月龄)双侧颈总动脉3个月,制备脑缺血模型.将大鼠分为四组:假手术组、模型组、NBP30和120 mg/kg.前两组灌胃给予植物油,后两组给予NBP,45 d后,用Morris水迷宫检测大鼠的空间认知能力.同时,取皮层和海马,用生化法检测超氧化物歧化酶(SOD)、胆碱乙酰基转移酶(ChAT)和真性胆碱酯酶(TChE)活力以及丙二醛含量. 结果 Morris水迷宫实验5天训练中,模型组逃避潜伏期变化很小,NBP小剂量组从(57.7±3.8)s缩短至(30.5±17.1)s,大剂量组从(58.4±1.8)s缩短至(28.9±11.3)s,与模型组比较差异有统计学意义(P＜0.05或P＜0.01).空间探索实验中,与模型组比较,NBP小剂量和大剂量组目标象限活动时间百分比明显增加,分别为(26.0±6.9)％和(27.3±5.3)％(P＜0.05).模型组皮层SOD升至(134.6±13.9)U/mg,NBP大剂量组降低为(112.3±7.6)U/mg(P＜0.01).与模型组比较,NBP小、大剂量皮层丙二醛减少,分别为(2.39±0.31) nmol/mg和(1.56±0.19) nmol/mg(P＜0.01).与模型组比较,NBP小、大剂量组海马丙二醛也减少,分别为(0.71±0.10) nmol/mg和(0.83±0.05)nmol/mg(P＜0.01).与模型组比较,NBP大剂量组皮层ChAT水平升高,为(1615±100) U/g(P＜0.05).与模型组比较,NBP小、大剂量海马ChAT水平也升高,分别为(1746±204)和(1697±117) U/g(P＜0.05). 结论 NBP通过减轻氧化应激损伤及增强胆碱能神经元的活性机理发挥改善慢性脑缺血大鼠空间认知缺陷的作用.
목적 관찰소선정분태(dl-NBP)대만성뇌결혈대서인지적개선작용,병연구기생화궤제. 방법 영구성결찰노령대서(15월령)쌍측경총동맥3개월,제비뇌결혈모형.장대서분위사조:가수술조、모형조、NBP30화120 mg/kg.전량조관위급여식물유,후량조급여NBP,45 d후,용Morris수미궁검측대서적공간인지능력.동시,취피층화해마,용생화법검측초양화물기화매(SOD)、담감을선기전이매(ChAT)화진성담감지매(TChE)활력이급병이철함량. 결과 Morris수미궁실험5천훈련중,모형조도피잠복기변화흔소,NBP소제량조종(57.7±3.8)s축단지(30.5±17.1)s,대제량조종(58.4±1.8)s축단지(28.9±11.3)s,여모형조비교차이유통계학의의(P＜0.05혹P＜0.01).공간탐색실험중,여모형조비교,NBP소제량화대제량조목표상한활동시간백분비명현증가,분별위(26.0±6.9)％화(27.3±5.3)％(P＜0.05).모형조피층SOD승지(134.6±13.9)U/mg,NBP대제량조강저위(112.3±7.6)U/mg(P＜0.01).여모형조비교,NBP소、대제량피층병이철감소,분별위(2.39±0.31) nmol/mg화(1.56±0.19) nmol/mg(P＜0.01).여모형조비교,NBP소、대제량조해마병이철야감소,분별위(0.71±0.10) nmol/mg화(0.83±0.05)nmol/mg(P＜0.01).여모형조비교,NBP대제량조피층ChAT수평승고,위(1615±100) U/g(P＜0.05).여모형조비교,NBP소、대제량해마ChAT수평야승고,분별위(1746±204)화(1697±117) U/g(P＜0.05). 결론 NBP통과감경양화응격손상급증강담감능신경원적활성궤리발휘개선만성뇌결혈대서공간인지결함적작용.
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 groups:sham,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.