不同剂量鱼藤酮对拟帕金森病模型大鼠行为学及纹状体多巴胺含量的影响

Impact of different dosage of rotenone on behavior and dopamine content in striatum of Parkinson like model rats

目的观察不同剂量鱼藤酮皮下注射对大鼠行为学及脑纹状体多巴胺含量的影响,探讨鱼藤酮拟帕金森病大鼠模型的适宜造模条件。方法 Lewis大鼠分别给予鱼藤酮不同剂量(1.0、1.5和2.0 mg/kg/d)皮下注射共28 d。应用旷场实验和斜板实验分别测定大鼠的运动功能和协调性,高效液相色谱-电化学法检测大鼠纹状体内多巴胺含量。结果模型组大鼠存活率随鱼藤酮注射剂量的升高呈逐渐下降趋势。鱼藤酮2.0 mg/kg组大鼠体重最先明显降低,随着注射时间的延长,各模型组大鼠均出现显著的体重降低。旷场实验结果显示,各剂量鱼藤酮组大鼠跨格次数和站立次数均明显下降。斜板实验结果显示,鱼藤酮1.5 mg/kg组大鼠在斜板的停留角度较对照组显著减小。鱼藤酮1.5 mg/kg组大鼠脑纹状体内多巴胺含量显著降低。结论鱼藤酮1.5 mg/kg皮下注射28 d,大鼠出现明显的运动功能障碍和脑内多巴胺含量减少,而死亡率相对较低,因此是建立帕金森病大鼠模型的适宜剂量。

Objective To observe the impact of different dosages of rotenone on behavior and dopamine content in stratium of rats, and explore the optimum experimental condition of PD rat model induced by rotenone injection. Methods The Lewis rats were subcutaneously injected by different dosage of rotenone （ 1.0, 1.5 and 2. 0 mg/kg/day） for 28 days. The open field and inclined plane tests were used to evaluate the movement function and coordination, respectively. High performance liquid chromatography-electrochemical method was used to measure the content of dopamine in striatum. Results The survival rate of model rats decreased with the increase of rotenone dosage. The body weight of all 3 model groups declined significantly in a dose-dependent manner. The number of lattice and the stand-up times in the open field test decreased obviously in 3 groups of rotenone rats. The maximum angle of plane in the inclined plane test declined significantly in rotenone 1.5 mg/kg group compared with control. The dopamine content in striatum of rats reduced markedly in rotenone 1.5 mg/kg group. Conclusion Chronic exposure of rotenone at the dosage of 1.5 mg/kg could reproduce the behavioral and neurochemical features of PD.