Fas相关死亡结构域蛋白基因沉默对帕金森病模型鼠黑质凋亡相关蛋白的影响
发布时间：2018-09-03 10:15
【摘要】：目的：探讨Fas相关死亡结构域蛋白(FADD)基因沉默对帕金森病(PD)大鼠行为学变化及黑质死亡受体(Fas)和半胱氨酸蛋白酶8(Caspase-8)表达的影响。 方法：应用化学修饰的干扰RNA及立体定向技术等,在制作PD模型前黑质内注入FADD siRNA、FADD siRNA阳性对照物或FADD siRNA阴性对照物。观察正常对照组、PD组、FADD siRNA组、FADD siRNA阳性对照组和FADD siRNA阴性对照组(每组各15只)大鼠阿朴吗啡诱导的旋转行为的改变；采用Western印迹分析和RT-PCR等方法,检测以上5组大鼠黑质FADD、Fas和Caspase-8蛋白及mRNA的半定量表达。 结果：正常对照组大鼠阿朴吗啡诱导下无旋转行为,其余4组旋转次数超过6r/min(持续30min)的大鼠分别为12(12/14)、3(3/13)、4(4/15)、11(11/14),组间比较差异具有统计学意义(χ2=18.56,P=0.000)；与正常组比较,PD组各个蛋白及mRNA的表达均明显升高：与PD组比较,FADD siRNA组FADD和Caspase-8蛋白及mRNA的表达受到明显抑制,差异具有统计学意义,但PD组和阴性对照组间及其余3组间比较差异均无统计学意义。与正常组比较,其余4组Fas蛋白及mRNA的表达均明显升高,差异具有统计学意义,但4组间比较差异无统计学意义。 结论：死亡受体凋亡通路在PD发病机制中起重要作用,而FADD siRNA能够有效抑制此通路,从而在一定程度上具有神经保护作用。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R742.5;R-332
本文编号：2219681
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R742.5;R-332
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