金钗石斛总生物碱改善链脲佐菌素所致大鼠海马神经元损伤  

Dendrobium nobile Lindl. alkaloids ameliorates streptozotocin-induced hippocampal neuron injury in rats

作　　者：巴智胜 蔡锐[1] 尹彩霞[1] 刘远贵 李小慧[1] 龚其海[1] 石京山[1] 李菲[1] 

机构地区：[1]遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099

出　　处：《中国新药与临床杂志》2017年第6期340-346,共7页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金资助项目(81560594);遵义医学院基金资助项目(F-612)

摘　　要：目的观察金钗石斛总生物碱(DNLA)对侧脑室内注射链脲佐菌素(STZ)诱导大鼠海马神经元损伤的作用。方法将50只雄性SD大鼠随机分为5组:空白对照组、空白给药组、模型组、低剂量组和高剂量组(每组n=10)。双侧侧脑室注射STZ建立大鼠海马神经元损伤模型,空白给药组、高剂量组每日1次灌胃DNLA 40 mg·kg^(-1),低剂量组每日1次灌胃DNLA 20 mg·kg^(-1),空白对照组及模型组灌胃等体积溶媒,连续给药28 d。Nissl染色观察海马神经元存活情况,Western blot检测糖原合成酶激酶3β(GSK-3β)、Tau蛋白、蛋白磷酸酶2A-α(PP2A-α)蛋白表达以及p-Ser9-GSK-3β、pY216-GSK-3β、pSer199-Tau、p-Ser396-Tau、p-Ser404-Tau、p-Ser422-Tau、p-Thr231-Tau水平。结果模型组较空白对照组大鼠海马CA3区存活神经元数目明显减少(P<0.01),海马p-Ser9-GSK-3β水平降低(P<0.05),pSer199-Tau、p-Ser396-Tau、p-Ser404-Tau、p-Ser422-Tau、p-Thr231-Tau水平增高(P<0.05)。高剂量组较模型组大鼠海马CA3区存活神经元数目明显增加(P<0.01),海马p-Ser9-GSK-3β水平上调及pSer199-Tau、p-Ser396-Tau、p-Ser404-Tau、p-Ser422-Tau、p-Thr231-Tau水平降低(P<0.05)。结论DNLA明显改善STZ诱导的大鼠海马神经元的损伤和丢失,并可激活GSK-3β,抑制Tau蛋白过度磷酸化。AIM To investigate the effect of Dendrobium nobile Lindl. alkaloids （DNLA） on the hippocampal neuron injury induced by bilateral intracerebroventricular （ICV） streptozotocin （STZ） injection in rats. METHODS Totally 50 male Sprague-Dawley rats were randomly divided into 5 groups： control, control ＋DNLA40, STZ, STZ ＋ DNLA20, and STZ ＋ DNLA40, n = 10 for every group. After a single ICV STZ injection, DNLA or vehicle was given by one time a day for 28 days. DNLA 40 mg·kg^-1 was administered to the control ＋ DNLA40 and STZ ＋ DNLA40 group, and 20 mg·kg^-1 was administered to the STZ ＋ DNLA20 group, and volume- matched vehicle was administered to the control and STZ group. Hippocampal neuron injury was observed after Nissl staining. The protein expression levels of glycogen-synthase kinase-3β （GSK-3β）, Tau, and protein phosphatase 2A-α（PP2A-α） and the levels of p- Ser9- GSK- 3β, pY216- GSK- 3β, p- Ser199 - Tau, p - Ser396 - Tau, p - Ser404 - Tau, p - Ser422 - Tau, and p - Thr231 - Tau were detected by Western blot. RESULTS ICV STZ injection significantly induced neuronal injury and loss in CA3 region （P 〈 0.01） , decreased the level of p- Ser9- GSK- 3β and elevated the levels of p- Ser199- Tau, p- Ser396- Tau, p- Ser404- Tau, p-Ser422-Tau, p-Thr231-Tau （P 〈 0.05） in the STZ group. Nevertheless, DNLA 40 mg-kg-1 treatment significantly ameliorate the STZ- induced hippocampal neuronal injury and loss （P 〈 0.05） , increased the level of p - Set9 - GSK - 3β and decreased the levels of p - Ser199 - Tau, p - Ser396 - Tau, p - Set404 - Tau, p - Ser422-Tau, p-Thr231-Tau （P 〈 0.05）. CONCLUSION DNLA can ameliorate the STZ-induced hippocampal neuron injury, up-regulate the activity of GSK-3β, and inhibit the hyperphosphorylation of Tau protein in rats.

关 键 词：金钗石斛 链脲菌素 糖原合成酶激酶3 TAU蛋白质类 海马 

分 类 号：R961[医药卫生—药理学]