雷帕霉素干预对左旋多巴诱发的异动症大鼠行为学的影响

发布时间：2018-10-15 09:21

【摘要】：目的研究雷帕霉素干预对左旋多巴诱发的异动症(LID)的行为学的影响。方法通过6-羟基多巴胺颅内立体定向注射制作偏侧大鼠帕金森病模型。给予左旋多巴腹腔注射1周制作LID大鼠模型。将LID大鼠分为LID对照组(LID组)和雷帕霉素干预观察组(RAPA组)。继续左旋多巴腹腔注射2周,RAPA组大鼠每天于左旋多巴注射前45 min腹腔注射雷帕霉素,低剂量0.25 mg/(kg·d)、中剂量0.35mg/(kg·d)、高剂量0.5 mg/(kg·d),每周注射4 d,持续2周。对照组同时给予等体积生理盐水腹腔注射。记录大鼠异常不自主运动(AIM)评分并对比分析。结果 RAPA低剂量亚组未观察到有意义的行为学改变;RAPA高剂量亚组在雷帕霉素给药后数天出现精神萎靡、食欲减退、血尿等症状,5~10 d左右逐渐死亡,经尸体解剖及病理切片发现,动物死亡原因与肺炎、肝肾损害等原因密切相关。RAPA中剂量亚组行为学改变比较理想,且动物耐受性较好,没有出现死亡。RAPA干预治疗开始起,RAPA中剂量亚组大鼠每天AIM评分均较LID组大鼠明显降低(均P0.05)。左旋多巴注射第20 d,RAPA中剂量亚组大鼠左旋多巴治疗后120 min内AIM评分均较LID组大鼠明显降低(均P0.05)。结论雷帕霉素治疗能显著改善LID大鼠行为学表现,改善LID大鼠不自主运动症状。
[Abstract]:Objective to study the effect of rapamycin on the behavior of (LID) induced by levodopa. Methods 6-hydroxydopamine stereotactic intracerebral injection was used to establish Parkinson's disease model in hemiparkinsonism rats. LID rat model was established by intraperitoneal injection of levodopa for 1 week. LID rats were divided into LID control group (LID group) and rapamycin intervention observation group (RAPA group). The rats in the RAPA group were injected rapamycin 45 min per day before L-dopa injection, and 0.35mg/ (kg d), at a low dose of 0.25 mg/ (kg d), at a high dose of 0.5 mg/ (kg d), was injected 4 days a week for 2 weeks. The control group was given intraperitoneal injection of the same volume of normal saline at the same time. The (AIM) score of abnormal involuntary movement in rats was recorded and compared. Results No significant behavioral changes were observed in the low dose subgroup of RAPA, but in the high dose subgroup of RAPA, symptoms such as mental retardation, loss of appetite and hematuria appeared a few days after administration of rapamycin, and died gradually for about 10 days, which were found by autopsy and pathological sections. The causes of animal death are closely related to pneumonia, liver and kidney damage, and so on. The behavioral changes of moderate dose subgroup of RAPA are ideal, and the animal tolerance is good. From the beginning of RAPA intervention, the daily AIM score of RAPA moderate dose subgroup was significantly lower than that of LID group (P0.05). The AIM scores in the middle dose subgroup were significantly lower than those in the LID group within 120 min after injection of L-dopa on the 20th day (P0.05). Conclusion rapamycin treatment can significantly improve the behavior of LID rats and improve the involuntary motor symptoms of LID rats.
【作者单位】：湖北省十堰市太和医院(湖北医药学院附属太和医院)神经康复科;海南医学院附属医院神经内科;江苏省宝应县人民医院神经内科;华中科技大学同济医学院附属协和医院神经内科;
【基金】：国家自然科学基金(31260241)
【分类号】：R749.94;R742.5

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