尿酸对帕金森病大鼠学习记忆能力的影响及其机制

Effects of uric acid on learning and memory ability of rats with of Parkinson disease and the mechanism

目的 探讨尿酸（UA）对六羟多巴胺（6-OHDA）诱导的SD大鼠帕金森病（PD）模型学习记忆能力的影响及其机制.方法 将雌性SD大鼠分为对照组（A组）、PD组（B组）、尿酸处理组（C1-C5组）,每组各15只;PD造模成功后第1～6天C1、C2、C3、C4、C5组分别腹腔注射0.1、1、5、10、20 ms/（ks·d）的尿酸,A、B组分别腹腔注射等剂量生理盐水.第3周对各组行Y型电迷宫测试.第4周断头处死大鼠,用分光光度计测定纹状体内脂质过氧化物丙二醛（MDA）含量,用免疫组织化学鉴定酪氨酸羟化酶（TH）、Caspase-3.结果 A组学习成绩平均为（4.12±1.57）次,记忆成绩平均为（3.17±1.19）次.与A组比较,B组和C1-C5组学习记忆能力明显下降（P〈0.01）,损毁侧纹状体内MDA含量明显增加,黑质TH阳性细胞计数明显减少,Caspase-3阳性细胞计数明显增多;与B组比较,C2、C3、C4组学习记忆能力明显增强（P〈0.01）,损毁侧损纹状体内MDA含量明显减少,黑质TH阳性细胞计数明显增多,Caspase-3阳性细胞计数明显减少,C1、C5与B组比较差异无统计学意义（P〉0.01）;同时C2、C3组与C1、C4、C5组比较差异有统计学意义（P〈0.01）.结论 PD大鼠学习记忆能力明显下降,适当剂量的尿酸可改善PD大鼠学习记忆能力,其机制可能与尿酸降低氧化应激,减少多巴胺能神经元凋亡,保护多巴胺能神经元有关.

Objective To investigate the effects of uric acid upon learning and memory ability of Sprague-Dawley（SD） rats with Parkinson disease （PD） induced by 6-OHDA and the mechanism. Methods Female SD rats were divided into control group （group A）, PD group （group B）, PD uric acid treatment group （group C1-C5） （n=15 each）. During the 1st to 6th day the rats in groups CI-C.5 were intraperitone-ally injected with 0.1, 1,5, 10.0, 20.0 mg/（kg·d） uric acid, and those in groups A, and B were intraperitoneally injected with equal doses of normal saline. At the third week, the rats in each group were subjected to Y-type electric maze test. At the fourth week all rats were decapitated. Malondialdehyde （MDA） content in striatum was measured by using spectrophotometer, and tyrosine hydroxylase （TH） and Caspase-3-positive neurons in substantia nigra were identified by immunohistochemistry. Results Average learning achievement in group A was （4.12±1.57） times, and memory performance was （3.17±1.19） times. As compared with group A, learning and memory ability in group B and groups C1-C5 was decreased significantly （P〈 0.01）, MDA content was increased on the affected side of the striatum, TH-positive cell counts decreased in the substantia nigra, and Caspase-3-positive cell counts increased. As compared with group B, learning and memory ability was significantly improved （P〈0.01）, the MDA content decreased on the affected side of the striatum, TH-positive cell counts increased in the substantia nigra, Caspase-3 positive cell counts decreased in groups C2, C3, and CA, but there was no significant difference between groups C1, C5 and group B （P〉0.01）. There was significant difference between groups C2, C3 and groups C1, C4, C5 （P〈0.01）. Conclusion Learning and memory ability in PD rats was significantly decreased, while appropriate doses of uric acid can improve the PD learning and memory ability, which may be related to its neuroprotective property by reducing the oxidative stress to decrease dopaminergic neuronal apoptosis, thus to protect the dopaminergic neurons.