【摘要】：目的：探討Fas相關(guān)死亡結(jié)構(gòu)域蛋白(FADD)基因沉默對(duì)帕金森病(PD)大鼠行為學(xué)變化及黑質(zhì)死亡受體(Fas)和半胱氨酸蛋白酶8(Caspase-8)表達(dá)的影響。 方法：應(yīng)用化學(xué)修飾的干擾RNA及立體定向技術(shù)等,在制作PD模型前黑質(zhì)內(nèi)注入FADD siRNA、FADD siRNA陽性對(duì)照物或FADD siRNA陰性對(duì)照物。觀察正常對(duì)照組、PD組、FADD siRNA組、FADD siRNA陽性對(duì)照組和FADD siRNA陰性對(duì)照組(每組各15只)大鼠阿樸嗎啡誘導(dǎo)的旋轉(zhuǎn)行為的改變；采用Western印跡分析和RT-PCR等方法,檢測(cè)以上5組大鼠黑質(zhì)FADD、Fas和Caspase-8蛋白及mRNA的半定量表達(dá)。 結(jié)果：正常對(duì)照組大鼠阿樸嗎啡誘導(dǎo)下無旋轉(zhuǎn)行為,其余4組旋轉(zhuǎn)次數(shù)超過6r/min(持續(xù)30min)的大鼠分別為12(12/14)、3(3/13)、4(4/15)、11(11/14),組間比較差異具有統(tǒng)計(jì)學(xué)意義(χ2=18.56,P=0.000)；與正常組比較,PD組各個(gè)蛋白及mRNA的表達(dá)均明顯升高：與PD組比較,FADD siRNA組FADD和Caspase-8蛋白及mRNA的表達(dá)受到明顯抑制,差異具有統(tǒng)計(jì)學(xué)意義,但PD組和陰性對(duì)照組間及其余3組間比較差異均無統(tǒng)計(jì)學(xué)意義。與正常組比較,其余4組Fas蛋白及mRNA的表達(dá)均明顯升高,差異具有統(tǒng)計(jì)學(xué)意義,但4組間比較差異無統(tǒng)計(jì)學(xué)意義。 結(jié)論：死亡受體凋亡通路在PD發(fā)病機(jī)制中起重要作用,而FADD siRNA能夠有效抑制此通路,從而在一定程度上具有神經(jīng)保護(hù)作用。
[Abstract]:Aim: to investigate the effects of Fas associated death domain protein (FADD) gene silencing on the behavioral changes and the expression of substantia nigra death receptor (Fas) and cysteine protease 8 (Caspase-8) in (PD) rats with Parkinson's disease. Methods: FADD siRNA,FADD siRNA positive control or FADD siRNA negative control were injected into the substantia nigra of PD model by chemically modified interfering RNA and stereotactic techniques. To observe the changes of apomorphine induced rotation behavior in PD group and FADD siRNA negative control group (15 rats in each group), the changes of apomorphine induced rotation behavior in PD group and FADD siRNA negative control group were observed by Western blot analysis and RT-PCR analysis, respectively. The semi-quantitative expression of FADD,Fas and Caspase-8 protein and mRNA in substantia nigra were detected. Results: there was no rotation behavior induced by apomorphine in the normal control group. The number of rotation times of the other four groups exceeded that of 6r/min (continuous 30min) was 12 (12 / 14) 3 / 13 (4 / 15) and 11 / 14 (11 / 14) respectively. The difference between the two groups was statistically significant (蠂 2 / 18. 56 P 0. 000). Compared with normal group, the expression of FADD and Caspase-8 protein and mRNA in PD group were significantly increased, and the expression of FADD and Caspase-8 protein and mRNA in siRNA group were significantly inhibited compared with PD group. But there was no significant difference between PD group and negative control group and the other three groups. Compared with the normal group, the expression of Fas protein and mRNA in the other four groups were significantly increased, the difference was statistically significant, but there was no significant difference among the four groups. Conclusion: death receptor apoptosis pathway plays an important role in the pathogenesis of PD, and FADD siRNA can effectively inhibit this pathway and thus has neuroprotective effect to some extent.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R742.5;R-332

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 張旺明;帕金森病與細(xì)胞凋亡[J];國(guó)外醫(yī)學(xué).神經(jīng)病學(xué)神經(jīng)外科學(xué)分冊(cè);1997年05期

2 趙丹;;FADD研究進(jìn)展[J];國(guó)際免疫學(xué)雜志;2006年03期

3 劉文;黃文芳;盧賢瑜;;死亡受體信號(hào)傳導(dǎo)途徑研究進(jìn)展[J];檢驗(yàn)醫(yī)學(xué)與臨床;2006年09期

4 亓愛芹;薛莉;謝安木;;死亡相關(guān)蛋白小分子干擾RNA對(duì)帕金森病大鼠黑質(zhì)酪氨酸羥化酶表達(dá)的影響[J];中國(guó)臨床神經(jīng)科學(xué);2011年02期

5 趙君;秦麗晨;李興強(qiáng);謝安木;;凋亡相關(guān)基因bax與Th蛋白在帕金森病大鼠黑質(zhì)和紋狀體細(xì)胞中的表達(dá)[J];實(shí)用醫(yī)學(xué)雜志;2008年10期

6 劉新紅;謝安木;吳化民;秦麗晨;;FADD在帕金森病大鼠的表達(dá)及臨床意義[J];泰山醫(yī)學(xué)院學(xué)報(bào);2007年02期

7 任含平,施廣霞;Fas信號(hào)轉(zhuǎn)導(dǎo)與其抑制機(jī)制[J];國(guó)外醫(yī)學(xué)(生理、病理科學(xué)與臨床分冊(cè));2004年04期

8 邱炯;李法琦;;半胱氨酸天冬氨酸蛋白酶與心血管疾病[J];中國(guó)臨床康復(fù);2005年43期

9 常青,王曉良;細(xì)胞色素C、線粒體與凋亡[J];中國(guó)藥理學(xué)通報(bào);2003年03期

10 曹非,孫圣剛,童萼塘,駱芳,李紅蓮,楊木蘭,朱海珍;6-羥基多巴胺誘發(fā)大鼠黑質(zhì)細(xì)胞凋亡的實(shí)驗(yàn)研究[J];中華神經(jīng)科雜志;2001年01期

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