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目的:研究化学毒物百草枯(PQ)是否影响π型谷胱苷肽转硫酶(GSTP1)mRNA表达。方法:采用原位杂交方法观察PQ处理的小鼠脑内GSTP1mRNA的分布。不同时间窗处死小鼠,于不同脑区提取总RNA,RT-PCR扩增GSTP1。结果:GSTP1mRNA在正常小鼠脑内广泛表达。大剂量PQ(50mg·kg-1)导致脑内各部位GSTP1mRNA杂交显色明显降低,黑质-纹状体区域尤其显著。PQ20mg·kg-1腹腔注射后3h,中脑黑质区域GSTP1mRNA表达与对照组比明显降低(P=0.026);18h时纹状体GSTP1mRNA表达比对照组显著下降(P=0.044)。PQ50mg·kg-1腹腔注射,3h后中脑黑质区域和纹状体区域GSTP1mRNA表达与对照组比显著减少(P值分别为0.024和0.034);18h时黑质和皮质GSTP1mRNA的表达与对照组比显著下降(P值分别为0.008和0.037)。结论:PQ可影响小鼠黑质-纹状体区域神经元GSTP1mRNA的表达。因此,本研究提示PQ可能通过GSTP1增加罹患PD的风险。
AIM: To investigate whether paraquat (PQ) affects the expression of π-glutathione S-transferase (GSTP1) mRNA. Methods: The distribution of GSTP1 mRNA in brain of PQ-treated mice was observed by in situ hybridization. Mice were sacrificed at different time windows and total RNA was extracted from different brain regions. GSTP1 was amplified by RT-PCR. Results: GSTP1 mRNA was widely expressed in normal mouse brain. Large doses of PQ (50mg · kg-1) resulted in a significant decrease in GSTP1 mRNA hybridization in all parts of the brain, especially in the substantia nigra and striatum. At 3h after PQ20mg · kg-1 intraperitoneal injection, the expression of GSTP1mRNA in midbrain substantia nigra was significantly lower than that in control group (P = 0.026). At 18h, the expression of GSTP1mRNA in striatum was significantly lower than that in control group (P = 0.044). PQ50mg · kg-1 intraperitoneal injection, 3h later, the expression of GSTP1mRNA in midbrain nigrostriatum and striatum was significantly decreased compared with the control group (P = 0.024 and 0.034, respectively); at 18h, the expression of GSTP1mRNA in substantia nigra and cortex was significantly lower than that in control group (P = 0.008 and 0.037, respectively). Conclusion: PQ can affect the expression of GSTP1mRNA in the substantia nigra and striatum of mice. Therefore, this study suggests that PQ may increase the risk of PD through GSTP1.