CAJ | 학술논문

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.
목적 탐토뇨산(UA)대륙간다파알(6-OHDA)유도적SD대서파금삼병(PD)모형학습기억능력적영향급기궤제.방법 장자성SD대서분위대조조(A조)、PD조(B조)、뇨산처리조(C1-C5조),매조각15지;PD조모성공후제1～6천C1、C2、C3、C4、C5조분별복강주사0.1、1、5、10、20 ms/(ks·d)적뇨산,A、B조분별복강주사등제량생리염수.제3주대각조행Y형전미궁측시.제4주단두처사대서,용분광광도계측정문상체내지질과양화물병이철(MDA)함량,용면역조직화학감정락안산간화매(TH)、Caspase-3.결과 A조학습성적평균위(4.12±1.57)차,기억성적평균위(3.17±1.19)차.여A조비교,B조화C1-C5조학습기억능력명현하강(P<0.01),손훼측문상체내MDA함량명현증가,흑질TH양성세포계수명현감소,Caspase-3양성세포계수명현증다;여B조비교,C2、C3、C4조학습기억능력명현증강(P<0.01),손훼측손문상체내MDA함량명현감소,흑질TH양성세포계수명현증다,Caspase-3양성세포계수명현감소,C1、C5여B조비교차이무통계학의의(P>0.01);동시C2、C3조여C1、C4、C5조비교차이유통계학의의(P<0.01).결론 PD대서학습기억능력명현하강,괄당제량적뇨산가개선PD대서학습기억능력,기궤제가능여뇨산강저양화응격,감소다파알능신경원조망,보호다파알능신경원유관.
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.