中国临床神经科学
中國臨床神經科學
중국림상신경과학
CHINESE JOURNAL OF CLINICAL NEUROSCIENCES
2014年
5期
496-503
,共8页
帕金森病%左旋多巴%树突状大分子%聚酰胺-胺树突状大分子%α-突触核蛋白
帕金森病%左鏇多巴%樹突狀大分子%聚酰胺-胺樹突狀大分子%α-突觸覈蛋白
파금삼병%좌선다파%수돌상대분자%취선알-알수돌상대분자%α-돌촉핵단백
Parkinson’s disease%L-dopa%dendrimer%poly amido-amine dendrimer%α-synuclein
目的构建左旋多巴-聚酰胺-胺(PAMAM)树突状大分子共轭体,评价其在α-突触核蛋白(α-Syn)纤丝化过程中的作用。方法采用左旋多巴对PAMAM树突状大分子进行表面修饰,合成端基改性产物左旋多巴- PAMAM树突状大分子共轭体。应用超视光谱和衰减傅里叶变换红外光谱仪(FTIR)鉴定左旋多巴-PAMAM树突状大分子共轭体合成,硫磺素含量测定及FTIR评价左旋多巴- PAMAM树突状大分子共轭体在α-Syn纤丝化中的作用。结果超视光谱和FTIR可以鉴定共轭体是否形成,相对于单独的左旋多巴及PAMAM树突状大分子,共轭体的FTIR峰值区域吸收增加。α-Syn与PAMAM树突状大分子共孵育后,与空白对照组(硫磺素+缓冲液)比较,其硫磺素荧光染色显著减少(P<0.05);与左旋多巴-PAMAM树突状大分子共轭体共孵育后,硫磺素荧光染色进一步减弱。α-Syn的FTIR显示,左旋多巴-PAMAM树突状大分子共轭体组随时间延长,峰值区域明显下降,且吸收率的差异发生在1636 cm-1和1655 cm-1。结论左旋多巴与PAMAM树突状大分子可以形成共轭体,左旋多巴-PAMAM树突状大分子共轭体显著抑制α-Syn纤丝化,且各时间点的效果均较单独应用左旋多巴或PAMAM树突状大分子更好。
目的構建左鏇多巴-聚酰胺-胺(PAMAM)樹突狀大分子共軛體,評價其在α-突觸覈蛋白(α-Syn)纖絲化過程中的作用。方法採用左鏇多巴對PAMAM樹突狀大分子進行錶麵脩飾,閤成耑基改性產物左鏇多巴- PAMAM樹突狀大分子共軛體。應用超視光譜和衰減傅裏葉變換紅外光譜儀(FTIR)鑒定左鏇多巴-PAMAM樹突狀大分子共軛體閤成,硫磺素含量測定及FTIR評價左鏇多巴- PAMAM樹突狀大分子共軛體在α-Syn纖絲化中的作用。結果超視光譜和FTIR可以鑒定共軛體是否形成,相對于單獨的左鏇多巴及PAMAM樹突狀大分子,共軛體的FTIR峰值區域吸收增加。α-Syn與PAMAM樹突狀大分子共孵育後,與空白對照組(硫磺素+緩遲液)比較,其硫磺素熒光染色顯著減少(P<0.05);與左鏇多巴-PAMAM樹突狀大分子共軛體共孵育後,硫磺素熒光染色進一步減弱。α-Syn的FTIR顯示,左鏇多巴-PAMAM樹突狀大分子共軛體組隨時間延長,峰值區域明顯下降,且吸收率的差異髮生在1636 cm-1和1655 cm-1。結論左鏇多巴與PAMAM樹突狀大分子可以形成共軛體,左鏇多巴-PAMAM樹突狀大分子共軛體顯著抑製α-Syn纖絲化,且各時間點的效果均較單獨應用左鏇多巴或PAMAM樹突狀大分子更好。
목적구건좌선다파-취선알-알(PAMAM)수돌상대분자공액체,평개기재α-돌촉핵단백(α-Syn)섬사화과정중적작용。방법채용좌선다파대PAMAM수돌상대분자진행표면수식,합성단기개성산물좌선다파- PAMAM수돌상대분자공액체。응용초시광보화쇠감부리협변환홍외광보의(FTIR)감정좌선다파-PAMAM수돌상대분자공액체합성,류광소함량측정급FTIR평개좌선다파- PAMAM수돌상대분자공액체재α-Syn섬사화중적작용。결과초시광보화FTIR가이감정공액체시부형성,상대우단독적좌선다파급PAMAM수돌상대분자,공액체적FTIR봉치구역흡수증가。α-Syn여PAMAM수돌상대분자공부육후,여공백대조조(류광소+완충액)비교,기류광소형광염색현저감소(P<0.05);여좌선다파-PAMAM수돌상대분자공액체공부육후,류광소형광염색진일보감약。α-Syn적FTIR현시,좌선다파-PAMAM수돌상대분자공액체조수시간연장,봉치구역명현하강,차흡수솔적차이발생재1636 cm-1화1655 cm-1。결론좌선다파여PAMAM수돌상대분자가이형성공액체,좌선다파-PAMAM수돌상대분자공액체현저억제α-Syn섬사화,차각시간점적효과균교단독응용좌선다파혹PAMAM수돌상대분자경호。
Aim To prepare and characterizeL-dopa-dendrimer conjugate, and evaluate its effect onα-synuclein ifbrillation of Parkinson’s disease.MethodsL-dopa was used to modify G4 poly amido-amine dendrimer (G4 PAMAM), and the modiifed product levodopa-dendrimer conjugate was synthesized. Fourier Transform Infrared Spectroscopy (FTIR) was used to confirm the synthesization ofL-dopa-dendrimer conjugate. The effect ofL-dopa-dendrimer conjugate on α-synuclein fibrillation was evaluated by Ultra-visible Spectroscopy and thioflavint assay andFTIR.Results There is also an increase in peak area observed in the region of FTIR inL-dopa-dendrimer conjugate compared to dendrimer orL-dopa alone.α-synuclein incubated with different drugs showed similar data that a signiifcant reduction in thiolfavint lfuorescence compared to the lfuorescence observed in the absence of the drugs, and withL-dopa-dendrimer conjugate was able to inhibit the AS fibrillation better. FTIR of α-synuclein withL-dopa -dendrimer conjugate showed that the peak area declined dramatically with respect to increase in time, and the differences in the area occurred in the absorbance around 1 636 cm-1 and 1 655 cm-1.ConclsionTheL-dopa and dendrimer might formL-dopa-dendrimer conjugate. The conjugate can be characterized by using Ultra-visible Spectroscopy and FTIR. Using thiolfavint assay and FTIR were able to measure the effect of the conjugate on α-synuclein fibrillation. And the data showed thatL-dopa-dendrimer conjugate significantly inhibitedα-synuclein ifbrillation (P<0.05) greater than dendrimer orL-dopa alone all the time.