目的探讨三七皂苷Rg₁对局灶性脑缺血-再灌注损伤大鼠大脑皮质中脑源性神经营养因子(BDNF)阳性蛋白的水平和阳性神经元数目是否具有上调作用。方法选取成年雄性SD大鼠60只,随机分为脑缺血-再灌注模型组、三七皂苷Rg₁高、中、低剂量(200、100、50 mg/kg)组和阳性对照(尼莫地平,1 mg/kg)组,采用线栓法制作大鼠局灶性脑缺血-再灌注模型,各组ig给药并分别于给药后1、3、7 d随机取4只大鼠,以灌注法取脑组织,冰冻法切片,免疫组织化学ABC法染色,用高清晰度彩色病理图文报告分析系统测量、分析各组大鼠大脑皮质中BDNF阳性蛋白的水平和阳性神经元数目的变化,并观察大鼠脑缺血-再灌注后的神经功能缺失症状。结果与模型组相比,三七皂苷Rg₁高、中、低剂量均能明显改善脑缺血-再灌注的神经功能缺失症状,并能上调大鼠脑缺血-再灌注损伤的大脑皮质中BDNF阳性蛋白的水平和阳性神经元数量(P<0.05);各剂量的作用强于或相当于阳性对照。结论三七皂苷Rg₁能上调BDNF阳性蛋白的表达,通过BDNF对脑缺血-再灌注神经元损伤所起的保护作用,从而发挥其对脑缺血的治疗作用。

Objective To explore the effects of notoginsenoside-Rg₁ on brain-derived neurotrophic factor(BDNF) protein in cerebrum cortex of MCAO/R injury,as well as to investigate whether notoginsenoside-Rg₁ can up-regulate the protein content of BDNF of the positive neurons or the amount of the po-sitive neurons.Methods Adult male SD rats(60) were randomly divided into model group,notoginsenoside-Rg₁ high,middle,and low dose(200,100,50 mg/kg) groups,and the positive control(Nimodipine,1 mg/kg) group.All drugs were given once a day by ip till the mouse was killed.The focal cerebral(ischemia-)reperfusion model was made with thread-occluded method.Their frozen brain tissue were sliced(into) section of 12 μm thickness.The four rats were randomly taken from each groups to be treated as specimens after surgical handle in 1,3,and 7 d.The slices were according to the immunohistochemical ABC techniques.The protein content of BDNF of the positive neurons and the amount of the positive neurons in cerebrum cortex of rat were observed and counted by HPIAS—1000 analytic system,and the nervous deficit symptoms after the cerebral ischemia were observed.Results Comparing with the model group,all notoginsenoside-Rg₁ treated groups obviously improved some nervous deficit symptoms of cerebral ischemia-reperfusion rats,and increased the protein content of BDNF and the amount of the positive neurons in the cerebrum cortex of model rats(P0.05).In different groups,the effect of notoginsenoside-Rg₁ was superior to that of Nimodipine or equated to it.Conclusion Notoginsenoside-Rg₁ could up-regulate the expression of BDNF and increase the amount of positive neurons in cerebrum cortex.It treated cerebral ischemia by the protection of BDNF on neurons injury in the focal cerebral ischemia-reperfusion,which can be one of the mechanism of the protection of notoginsenoside-Rg₁ on focal cerebral(ischemia) reperfusion injury.

云南省自然科学基金项目(2002C0051m)