参乌胶囊对拟亨廷顿病大鼠行为及脑内神经营养因子的影响

Effects of Shenwu Capsules on the Behavior and Neurotrophic Factors in the Rats with Mimic Huntington's Disease

目的 观察拟亨廷顿病模型大鼠学习记忆改变情况 ,脑黑质、海马部位脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子 (GDNF)的改变情况及参乌胶囊对其的干预作用。方法 用线粒体呼吸链复合体Ⅱ /Ⅲ抑制剂——— 3-硝基丙酸 (3 nitropropionicacid ,3 NPA) 2 0mg/kg对SD大鼠隔日腹腔注射连续造模 2 0d ,建立HD大鼠模型。造模的同时 ,用药组大鼠给予参乌胶囊连续灌胃 2 5d。阳性对照药组自造模当日起给予氟哌啶醇。应用Morris水迷宫及避暗实验检测大鼠学习记忆能力。应用免疫组织化学染色法检测大鼠海马CA1及CA4区BDNF、GDNF的细胞数量及细胞面积。结果 Morris水迷宫实验中 ,模型大鼠的游出时间及游出距离较对照组明显延长 ,参乌胶囊用药组可以显著缩短大鼠的游出时间及距离。避暗实验中 ,参乌胶囊用药组大鼠较模型大鼠进入暗箱的潜伏期分别显著性延长 5 6 6 9s和 5 4 2 4s。在海马CA1及CA4区 ,模型组动物BDNF、GDNF阳性细胞的表达明显较正常对照组细胞数减少 ,阳性细胞总面积减少。而 96 2中剂量组对于此区BDNF、GDNF阳性细胞的表达明显具增强作用 (P <0 0 1)。结论 参乌胶囊可以明显增强动物学习记忆能力 ,增强 3 NPA模型大鼠海马处BDNF及GDNF的表达。

Objective To observe the changes in the abilities of learning and memory and the changes of (the brain derived neurotrophic factor) BDNF and (the glial cell line derived neurotrophic factor) GDNF in the of substantia nigra and hippocampus in the rat model of mimic Huntington's disease, and to observe the interfering effects of Shenwu Capsules (SC) on these changes. Methods The SD rat model of Huntington's disease was established by peritoneal injection of 3 nitropropionic acid, the mitochondrial respiratory chain complex Ⅱ/Ⅲ inhibitor, 20 mg/kg, once every other day, successively for 20 days. During the period of establishing the model, the rats in the treating group were intragastrically given SC successively for 25 days. The rats in the positive control group were given haloperidol on the first day when the model inducement began. The Morris water maze and step through tests were used to test the rat's abilities of learning and memory. The immunohistochemical staining was used to detect the numbers and areas of the BDNF positive and GDNF positive neurons in the CA1 and CA4 areas of the hippocampus. Results The results of Morris water maze test showed that the swimming time and distance of the rats in the model group were markedly prolonged as compared with those in the rats in the control group, and SC could remarkably shorten the swimming time and distance of the rats. The results of the step through test showed that the latency for going into the dark chamber in the rats in the middle SC dose group and large SC dose group was prolonged for 56.69 and 54.24 seconds respectively as compared with that in the rats in the model group. The numbers of the expressions of the BDNF positive and GDNF positive neurons in the hippocampal CA1 and CA4 areas of the rats in the model group were less than those in the rats in the normal control group, and the total stained area of the positive neurons also became decreased; but the expressions of the BDNF positive and GDNF positive neurons were markedly enhanced in the same hippocampal areas in the rats in the middle SC dose ( P >0 01). Conclusion SC can remarkably enhance the abilities of learning and memory of the rats and increase the expressions of BDNF and GDNF in the hippocampus.