百草枯急性干预对小鼠π型谷胱苷肽转硫酶mRNA表达的影响

Analysis of GSTP1 mRNA Expression in the Mice with Paraquat Treatment

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 the expression of P-type of glutathione S-transferase （GSTP1） after the paraquat （ PQ ） treatment. Methods： We explored the difference of various brain-areas of mice after PQ treatment by in situ hybridization. Total RNA was isolated from different brain areas at various time points and used for RT-PCR analysis. Results： GSTP1 mRNA was much abundant in many areas of brain of mice. PQ （ 50 mg·kg^-1 ） can cause significant decrease the expression of GSTPlmRNA in the all areas of brain; in particular, there were fewer positive cells in substantia nigra-striatum. The RT-PCR results showed that the levels of GSTP1 mRNA were strikingly reduced compared with the controls in substantia nigra after 3 h with 20 mg·kg^-1 PQ treatment （P=0.026）. After 18 h, the levels of GSTP1 mRNA were greatly decreased compared with the controls in triatums （ P=0.044 ）. The levels of GSTP1 mRNA were significantly reduced compared with the controls in after 3 h with 50 mg·kg^-1 PQ treatment （P=0.024, 0.034, respectively ）. After 18 h, the levels of GSTPlmRNA were decreased compared with the controls in substantia nigra and cortex （P=0.008, 0.037, respectively ）. Conclusion： PQ can inhibit the expression of the GSTP1 mRNA of substantia nigra and striatum of mice. It was suggested that the paraquat might increase the risk of suffering Parkinson＇s disease by inhibiting GSTP1 pathways.