内质网应激在PFOS致大鼠肝损伤中的作用

通过全氟辛烷磺酸(PFOS)28 d大鼠经口染毒评价PFOS肝损伤效应,探讨内质网应激在PFOS毒效应中的作用。Wistar大鼠随机分组,分别以0 mg·kg~(-1)、5 mg·kg~(-1)和10 mg·kg~(-1)PFOS灌胃染毒28 d。HE染色观察大鼠肝脏形态改变。ELISA法测定各组丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)和淀粉酶(AMY)含量变化。紫外分光光度法测定肝组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性变化。RT-PCR检测肝脏内质网应激标志蛋白表达水平。结果表明,PFOS造成大鼠体重降低、肝重增高(P0.05),组织切片显示肝细胞出现脂质沉积。PFOS不同剂量组大鼠ALT随暴露浓度增加,分别为(50.96±10.02)U·L~(-1)、(71.73±11.55)U·L~(-1),显著高于对照组(P0.05),AST、ALP含量与对照组相比显著上升(P0.05),高剂量组AMY水平为(833.46±63.05)U·L~(-1),与对照组相比显著降低(P0.05)。GSH-Px和SOD水平随PFOS浓度增加出现了显著降低(P0.05),而MDA水平显著升高(P0.05)。内质网应激标志蛋白表达均较对照组显著上升(P0.05)。以上结果说明PFOS可导致大鼠肝细胞损伤,其机制可能与内质网应激调控有关。

Effects of Endoplasmic Reticulum Stress on Perfluorooctane Sulfonate Induced Liver Damage in Rat

Effect of endoplasmic reticulum stress on perfluorooctane sulfonate induced liver damage in rat was investigated. Male rats were exposed by gavage with 0 mg?kg^-1, 5 mg?kg^-1 and 10 mg?kg^-1 PFOS for 28 days. Rats were sacri?ced and histological changes of the liver tissue were examined. The contents including ALT, AST, ALP and AMY in serum were determined by ELISA kits. MDA, SOD and GSH-Px were detected by the colorimetric method. Besides, expression of endoplasmic reticulum stress related genes was measured using real-time PCR.The present study showed that PFOS produced significant reductions in body weight gain in male rats. Liver/body weight value was significantly elevated relative to control in male rats. PFOS exposure resulted in a significant hepatic injury with cell edema and hypertrophy in both groups (P<0.05). ALT concentration was highest in 10 mg?kg^-1 group ((50.96±10.02) U?L^-1, (71.73±11.55) U?L^-1, respectively) while the content of AMY was lowest in 10 mg?kg^-1 group ((833.46±63.05) U?L^-1). Furthermore, compared with the control, ALP and AST increased significantly(P<0.05). Moreover, PFOS exposure reduced the levels of SOD and GSH-Px while increased the levels of MDA (P<0.05). Furthermore, results from RT-PCR revealed that PFOS up-regulated the expression level of GRP78 and CHOP. In conclusion, exposure to PFOS disturbed the liver homeostasis of male rats, and the mechanism of action is related to endoplasmic reticulum stress.