【摘要】：目的研究雷帕霉素干預(yù)對(duì)左旋多巴誘發(fā)的異動(dòng)癥(LID)的行為學(xué)的影響。方法通過6-羥基多巴胺顱內(nèi)立體定向注射制作偏側(cè)大鼠帕金森病模型。給予左旋多巴腹腔注射1周制作LID大鼠模型。將LID大鼠分為L(zhǎng)ID對(duì)照組(LID組)和雷帕霉素干預(yù)觀察組(RAPA組)。繼續(xù)左旋多巴腹腔注射2周,RAPA組大鼠每天于左旋多巴注射前45 min腹腔注射雷帕霉素,低劑量0.25 mg/(kg·d)、中劑量0.35mg/(kg·d)、高劑量0.5 mg/(kg·d),每周注射4 d,持續(xù)2周。對(duì)照組同時(shí)給予等體積生理鹽水腹腔注射。記錄大鼠異常不自主運(yùn)動(dòng)(AIM)評(píng)分并對(duì)比分析。結(jié)果 RAPA低劑量亞組未觀察到有意義的行為學(xué)改變;RAPA高劑量亞組在雷帕霉素給藥后數(shù)天出現(xiàn)精神萎靡、食欲減退、血尿等癥狀,5~10 d左右逐漸死亡,經(jīng)尸體解剖及病理切片發(fā)現(xiàn),動(dòng)物死亡原因與肺炎、肝腎損害等原因密切相關(guān)。RAPA中劑量亞組行為學(xué)改變比較理想,且動(dòng)物耐受性較好,沒有出現(xiàn)死亡。RAPA干預(yù)治療開始起,RAPA中劑量亞組大鼠每天AIM評(píng)分均較LID組大鼠明顯降低(均P0.05)。左旋多巴注射第20 d,RAPA中劑量亞組大鼠左旋多巴治療后120 min內(nèi)AIM評(píng)分均較LID組大鼠明顯降低(均P0.05)。結(jié)論雷帕霉素治療能顯著改善LID大鼠行為學(xué)表現(xiàn),改善LID大鼠不自主運(yùn)動(dòng)癥狀。
[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.
【作者單位】： 湖北省十堰市太和醫(yī)院(湖北醫(yī)藥學(xué)院附屬太和醫(yī)院)神經(jīng)康復(fù)科;海南醫(yī)學(xué)院附屬醫(yī)院神經(jīng)內(nèi)科;江蘇省寶應(yīng)縣人民醫(yī)院神經(jīng)內(nèi)科;華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬協(xié)和醫(yī)院神經(jīng)內(nèi)科;
【基金】：國(guó)家自然科學(xué)基金(31260241)
【分類號(hào)】：R749.94;R742.5

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