GSTP1基因低表达与全氟辛烷磺酸致大鼠肝脏氧化损伤的关系研究

Correlation of down-regulation of GSTP1 gene expression and oxidative injury from perfluorooctane sulfonate exposure in the liver of rats

目的探讨GSTP1基因低表达与全氟辛烷磺酸(PFOS)暴露致大鼠肝脏氧化损伤的关系,及其在PFOS肝毒性中的作用。方法 40只健康雄性SD大鼠随机分为空白对照组和PDFOS 0.5、5.0、20 mg/kg·bw·d 3个剂量组,经口灌胃染毒90 d,1次/d。染毒期间观察动物的毒性反应,检测肝脏病理改变及超微结构变化;硫代巴比妥酸法检测脂质过氧化产物MDA含量及总抗氧化能力T-AOC活性;荧光定量PCR方法检测GSTP1基因mRNA表达情况。结果 0.5、5.0和20 mg/kg·bw·d剂量组染毒大鼠均出现体重下降、精神状态差和躁动易激惹等中毒体征,20 mg/kg·bw·d剂量组体重降低明显、肝脏系数增加(P<0.01)。病理形态学发现各剂量组大鼠肝细胞不同程度的肿胀、胞浆空泡化及囊泡样脂滴沉积等毒性病理改变。与对照组比较,5.0和20 mg/kg·bw·d剂量组肝脏MDA含量显著升高(P<0.01),伴随T-AOC活性降低。Real-time PCR结果显示,肝脏GSTP1基因mRNA表达水平在PFOS中、高剂量组呈现下降趋势,20 mg/kg·bw·d组下调明显(P<0.05)。GSTP1 mRNA表达水平与MDA含量呈显著负相关(r=-0.307,P=0.028)。结论 PFOS暴露大鼠肝脏组织的GSTP1 mRNA表达水平下调。GSTP1基因转录抑制可能加剧肝脏氧化损伤发生发展,与PFOS的肝脏毒性有关。

Objective To explore the correlation between the expression of enzymes GSTP1 and liver toxicity from PFOS exposure.Methods 40 SD rats were exposure to PFOS at doses of 0,0. 5 mg/kg·bw·d,5. 0 mg/kg·bw·d and 20 mg/kg·bw·d by gavage daily for a period of 90 days. The toxic signs,body weight,organ coefficient and pathological lesion of liver organ of rats were observed. The lipid peroxidation product content of MDA and antioxidant capacity of T-AOC in liver were detected by TBA,as well as the expressions of GSTP1 mRNA assayed by RT-PCR. Results The pathological changes such as apparent hepatocytic hypertrophy,cytoplasmic vacuolation,lipid droplet and focal hydropic necrosis were observed in rat liver exposed to PFOS. Compared with control group,rat weights were reduced and liver coefficient were increased markedly in 0. 5 mg/kg·bw·d,5. 0 mg/kg·bw·d and 20 mg/kg·bw·d groups（P 〈0. 01）. The content of MDA were significantly higher than control group and followed with T-AOC ability decreased in rat liver of 5. 0 mg/kg·bw·d and20 mg/kg·bw·d groups. Compared with control group,the expression levels of GSTP1 mRNA were decreased and significantly downregulated in 20 mg/kg·bw·d group（P〈0. 05）. The expression of GSTP1 mRNA was negatively correlated with the content of MDA（r =-0. 307,P = 0. 028）. Conclusion The expression of GSTP1 mRNA is significantly down-regulated in rat liver from PFOS-exposure. The transcriptional repression of gene GSTP1 is associated with oxidative damage in PFOS-exposed liver.