尿酸对6-羟基多巴胺致大鼠黑质纹状体系统毒性的影响

目的 评价尿酸对6-羟基多巴胺致大鼠黑质纹状体系统多巴胺能神经元毒性的影响.方法 30只雄性SD大鼠,分为生理盐水组(10只)、100 mg/kg尿酸组(5只)、200 mg/kg尿酸组(10只)和250 mg/kg尿酸组(5只).每天2次(间隔2 h),每次腹腔注射生理盐水或尿酸5 d,于第6天第1次腹腔注射生理盐水或尿酸后,在立体定向仪指导下,右侧纹状体内两点注射6-羟基多巴胺.此后继续给予大鼠腹腔注射生理盐水或尿酸5 d.于注射6-羟基多巴胺后第3、4周分别进行自主活动计数,安非他明旋转实验,前肢功能测定.注射6-羟基多巴胺后第5周进行纹状体多巴胺和高香草酸水平测定.结果 200 mg/kg尿酸组大鼠自主活动计数(14±4)次/2 min]明显高于生理盐水组(4±5)次/2 min,P＜0.01];安非他明诱导的旋转实验100 mg/kg尿酸组(11.2 ±4.2)和200 mg/kg尿酸组每分钟旋转次数(10.8±7.5)显著低于生理盐水组(19.3 ±5.2,P＜0.01).200 mg/kg尿酸组前肢功能测定5 s内移动90 cm的前患肢步数(9.89±3.41)明显高于生理盐水组(4.36±3.72,P＜0.01);200 mg/kg尿酸组毁损侧纹状体多巴胺(0.29±0.19)、高香草酸水平(1.22±0.5)显著高于生理盐水组多巴胺(0.05 ±0.03,P＜0.01)、高香草酸水平(0.24±0.13,P＜0.05).结论 适当提高体内的尿酸水平能减轻6-羟基多巴胺对SD大鼠黑质纹状体系统多巴胺神经元的毒性作用.

Protective effects of uric acid on nigrostriatal system injury induced by 6-hydroxydopamine in rats

Objective To investigate the protective effects of uric acid on nigrostriatal system injury induced by 6-hydroxydopamine in rats. Methods Thirty male SD rats were divided into four groups. Uric acid of 100 mg/kg, 200 mg/kg, 250 mg/kg were injected intrapefitoneally (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, 6hydroxydopamine was injected into striatum to establish Parkinsen's disease (PD) model in rats. Then uric acid was injected ip into three groups and saline into controls for five days. Locomotion test, amphetamineinduced 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. Results 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 significanfly 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). Conclusion An appropriately elevated level of uric acid may protect the dopamine neuron of nigrostriatal system from injury of 6-hydroxydopamine in rats.