本文選題：帕金森病　切入點(diǎn)：cystatin　出處：《中國科學(xué)院研究生院（上海生命科學(xué)研究院）》2005年博士論文

【摘要】：我們通過microarray 和消減抑制雜交的方法獲得帕金森病紋狀體內(nèi)差異表達(dá)的200 左右基因,經(jīng)Northern、RT-PCR、原位雜交和免疫組化進(jìn)一步鑒定,獲得上調(diào)及下調(diào)的基因18 個。我們對其中幾個感興趣的基因cystatin C,trophinin,bystin 做了進(jìn)一步的研究。 Cystatin C 是II 型半胱氨酸蛋白酶(cysteine protease)抑制劑家族中(cystatins)的一個成員, Northern blot 結(jié)果顯示它在6-OHDA 損毀的大鼠紋狀體中持續(xù)上調(diào)。原位雜交和免疫組化結(jié)果也同樣證實(shí)Cystatin C 在6-OHDA 損毀的大鼠紋狀體中差異表達(dá),免疫熒光雙標(biāo)結(jié)果表明它來源于多種細(xì)胞成分,即神經(jīng)元、星型膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞。Cystatin C 對體外培養(yǎng)的E14 腹側(cè)中腦多巴胺能神經(jīng)元有促進(jìn)存活作用。體內(nèi)實(shí)驗(yàn)同樣證實(shí)了cystatin C 對6-OHDA 損毀的大鼠多巴胺能神經(jīng)元的存活作用。 Trophinin 和Bystin 曾被報(bào)道作為一個在胚胎著床過程中起重要作用的粘 附分子,但該分子在中樞神經(jīng)系統(tǒng)中的存在和作用從未有過報(bào)道。我們的結(jié)果表 明在6-OHDA 損傷的PD 大鼠中,Trophinin 和bystin 在黑質(zhì)和紋狀體中的表達(dá) 具有明顯的時(shí)空特點(diǎn),提示它們在中樞神經(jīng)系統(tǒng)具有某種作用。
[Abstract]:We obtained about 200 differentially expressed genes in the striatum of Parkinson's disease by microarray and subtractive suppression hybridization, which were further identified by Northern RT-PCR, in situ hybridization and immunohistochemistry. A total of 18 up-regulated and down-regulated genes were obtained, and several of them were further studied. Cystatin C is a member of the cysteine protease II inhibitor family. Northern blot results show that Cystatin C is up-regulated in the striatum damaged by 6-OHDA. The results of in situ hybridization and immunohistochemistry also confirm the presence of Cystatin C in 6-OHDA. Differential expression in the damaged rat striatum, Immunofluorescence double labeling results showed that it originated from a variety of cell components, namely neurons, Astrocytes and microglia. Cystatin C promoted the survival of dopaminergic neurons in the ventral mesencephalon of E14 cultured in vitro. The in vivo experiments also confirmed the survival of cystatin C on the dopaminergic neurons damaged by 6-OHDA in rats. Trophinin and Bystin have been reported as a adhesion molecule that plays an important role in embryo implantation. However, the presence and role of this molecule in the central nervous system have never been reported. Our results show that the expression of Trophinin and bystin in substantia nigra and striatum of PD rats damaged by 6-OHDA has obvious temporal and spatial characteristics. These results suggest that they play a role in the central nervous system.
【學(xué)位授予單位】：中國科學(xué)院研究生院（上海生命科學(xué)研究院）
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R-332

【共引文獻(xiàn)】

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