Wang Li-jun, Luo Wei-feng, Wang Heng-hui, Ni Gui-hua, Ye Yan, Li Dan, Liu Chun-feng
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhonghua Yi Xue Za Zhi. 2010 May 18;90(19):1362-5.
To investigate the protective effects of uric acid on nigrostriatal system injury induced by 6-hydroxydopamine in rats.
Thirty male SD rats were divided into four groups. Uric acid of 100 mg/kg, 200 mg/kg, 250 mg/kg were injected intraperitoneally (ip) into 5, 10, 5 rats twice daily at a 2-hour interval for five days and saline was injected ip into 10 rats as controls. At Day 6, 6-hydroxydopamine was injected into striatum to establish Parkinson's disease (PD) model in rats. Then uric acid was injected ip into three groups and saline into controls for five days. Locomotion test, amphetamine-induced rotation and forepaw adjusting step test were performed at Weeks 3 and 4 respectively after injection of 6-hydroxydopamine. HPLC-MS/MS was performed to detect the contents of dopamine and its metabolite homovanillic acid (HVA) in striatum at Week 5.
The scores of locomotion in 2 minutes of 200 mg/kg uric acid group (14 +/- 4/2 min) was higher significantly than saline group (4 +/- 5/2 min, P < 0.01). The amphetamine-induced rotation number in the 200 mg/kg uric acid group (10.8 +/- 7.5) was lower significantly that in the saline group (19.3 +/- 5.2, P < 0.01). Forepaw adjusting step test scores of 200 mg/kg uric acid group were higher significantly than those in the saline group (9.89 +/- 3.41 vs 4.36 +/- 3.72, P < 0.01). HPLC-MS/MS showed that the contents of DA (0.29 +/- 0.19) and HVA (1.22 +/- 0.5) in injured striatum of 200 mg/kg uric acid group were higher significantly than those in the saline group (0.05 +/- 0.03, P < 0.01; 0.24 +/- 0.13, P < 0.05).
An appropriately elevated level of uric acid may protect the dopamine neuron of nigrostriatal system from injury of 6-hydroxydopamine in rats.
探讨尿酸对6-羟基多巴胺诱导的大鼠黑质纹状体系统损伤的保护作用。
将30只雄性SD大鼠分为四组。分别将100mg/kg、200mg/kg、250mg/kg的尿酸腹腔注射（ip）到5只、10只、5只大鼠体内，每天两次，间隔2小时，共注射5天；将生理盐水腹腔注射到10只大鼠体内作为对照。在第6天，将6-羟基多巴胺注射到纹状体以建立大鼠帕金森病（PD）模型。然后对三组大鼠腹腔注射尿酸，对照组注射生理盐水，持续5天。分别在注射6-羟基多巴胺后的第3周和第4周进行运动测试、阿扑吗啡诱导的旋转试验和前爪调整步幅试验。在第5周，采用高效液相色谱-串联质谱法（HPLC-MS/MS）检测纹状体中多巴胺及其代谢产物高香草酸（HVA）的含量。
200mg/kg尿酸组2分钟运动评分（14±4/2分钟）显著高于生理盐水组（4±5/2分钟，P<0.01）。200mg/kg尿酸组阿扑吗啡诱导的旋转次数（10.8±7.5）显著低于生理盐水组（19.3±5.2，P<0.01）。200mg/kg尿酸组前爪调整步幅试验评分显著高于生理盐水组（9.89±3.41比4.36±3.72，P<0.01）。HPLC-MS/MS显示，200mg/kg尿酸组损伤纹状体中多巴胺（0.29±0.19）和HVA（1.22±0.5）的含量显著高于生理盐水组（0.05±0.03，P<0.01；0.24±0.13，P<0.05）。
适当升高尿酸水平可能保护大鼠黑质纹状体系统的多巴胺能神经元免受6-羟基多巴胺的损伤。
