發(fā)布時(shí)間：2018-09-03 10:15

【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(yáng)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(yáng)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(wú)旋轉(zhuǎn)行為,其余4組旋轉(zhuǎn)次數(shù)超過(guò)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(wú)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(wú)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

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