摘要
目的探讨更简便、更稳定的鱼藤酮诱导帕金森病大鼠模型的制作方法。方法制作鱼藤酮葵花油乳化液,分别通过连续1周、2周及3周背部皮下注射鱼藤酮(1.5 mg·kg-1·d-1)的方法给三组雄性SD大鼠用药,并与正常对照组及葵花油对照组比较,于1周、2周及3周分别观察并评价相应的三个鱼藤酮组的大鼠的行为学、中脑黑质的病理学以及酪氨酸羟化酶(tyrosine hydroxylase,TH)的免疫活性的改变。结果低剂量(1.5 mg·kg-1·d-1)长期背部皮下注射鱼藤酮可诱导雄性SD大鼠出现行为学、中脑黑质的病理学以及TH的免疫活性的改变,其变化程度均与持续用药时间密切相关。行为学评分神经功能缺损评分(mNSS)在三个模型组与两个对照组之间以及三个模型组两两之间的比较均有统计学差异(P<0.05),且评分与用药时间的相关系数为0.848;在病理学上,与两对照组相比,三个模型组中脑黑质神经元数量减少,残存神经元变性,可见嗜酸性小体;在TH免疫活性上,与正常对照组相比,三个模型组的大鼠黑质的TH阳性细胞均明显减少(t=29.882、44.799、59.697,P=0.000、0.000、0.000),均有统计学差异,且TH阳性细胞计数与用药时间的相关系数为-0.958。此模型成功率为62.5%,死亡率为18.75%,18.75%的大鼠对鱼藤酮不敏感。结论以1.5 mg·kg-1·d-1的鱼藤酮剂量对雄性SD大鼠进行诱导,持续用药3周可成功制作出鱼藤酮帕金森病大鼠模型,且该模型操作简便、费用少、成功率高。
Objective To investigate an easier and more stable method to reproduce the rotenone model of Parkinson＇ s disease in rats. Methods Rotenone, which was emulsified in sunflower oil, was injected subcutaneously to the back of rats in three groups of rotenone models. They were administered by rotenone（ 1.5 mg·kg--1· d-1）once daily for 7,14 and 21 days respectively and successively. Compared with normal control group and vehicle group, three groups of rotenone models were observed and evaluated the changes of behavior,pathology and tyrosine hydroxylase（TH） immunoreactivity in SNc at 7,14 and 21 days respectively. Results Male SD rats, which were injected subcutaneously with rotenone （1.5 mg ~ kg-1 d -＇ ） for 3 weeks, could reproduce the changes of behavior, pathology and TH immunoreactivity in SNc. These changes varied with the successively administered time closely. Compared with normal control groups, the behavioral score modified neurological severity（mNSS） of three model groups all had significant differences （ P 〈 0. 05 ）. And among three model groups, mNSS of each two groups also had significant differences. The correlation index between mNSS and medication time was 0. 848. Compared with two control groups, the pathological changes of three model groups included that the reduction of neurons in substantia nigra, degeneration of remaining neurons and appearance of Lewy body. Compared with two control groups, all the numbers of TH active ceils in three model groups were decreased obviously and had significant differences （t = 29. 882,44. 799,59. 697 respectively, and P = 0. 000,0. 000,0. 000 respectively）. The correlation index between the numbers of TH active cells and medication time was - 0. 958. The success rate of this model was 62. 5% ,and death rate was 18.75% ,while 18. 75% of rats were not sensitive to rotenone. Conclusion By the way of injecting rotenone（ 1.5 mg ~ kg-1 . d-I ）subcutaneously to the back of male SD rats for 3 weeks,rotenone model of PD in rats could be reproduced successfully. Conveniently operation, less cost and high achievement ratio are there advantages of this method.
出处
《中华脑科疾病与康复杂志（电子版）》
2013年第4期27-31,共5页
Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）
