全氟辛烷磺酸对小鼠大脑谷氨酸含量和蛋白激酶活性的影响

目的 通过观察全氟辛烷磺酸（PFOS）对雄性小鼠大脑谷氨酸含量、蛋白激酶C（PKC）和蛋白激酶A（PKA）活性的影响及超微结构的改变,探讨PFOS所致神经毒性机制。方法 44只雄性昆明系小鼠按体重分为4组,每组11只。PFOS染毒剂量分别为5、10、20mg／kg,对照组给予同等体积2％吐温．80,连续经口染毒10d。分光光度计法测定小鼠大脑谷氨酸含量,非放射性蛋白激酶检测法测定PKC和PKA活性,透射电镜观察大脑皮质超微结构的损伤。结果 10、20mg／kg染毒组小鼠大脑谷氨酸含量分别为（1．57±0．11）、（1．62±0．16）mmol/g蛋白,与对照组（1．45±0．13）mmol/g蛋白]相比,差异有统计学意义（F=39．59,P〈0．05）;5、10、20mg／kg染毒组PKC活性分别为（29．05±2．89）、（33．65±3．82）和（34．20±3．16）pmol·min^-1·（mg蛋白）^-1,与对照组（24．53±2．88）pmol·min^-1·（mg蛋白）^-1]比较,差异有统计学意义（F=7．75,P〈0．05）。5、10、20mg／kg染毒组PKA活性与对照组比较,分别升高了（24．12±3．86）％、（34．02±3．04）％和（33．42±3．71）％,差异有统计学意义（F=26．27,P〈0．01）。但PKC和PKA活性的升高趋势在PFOS剂量为20mg／kg时趋缓。给予小鼠PFOS可对大脑皮质细胞造成细胞核膜凹陷的超微结构损伤。结论 PFOS染毒导致小鼠脑组织谷氨酸含量、PKC和PKA活性升高,并对大脑皮质细胞造成超微结构损伤,可能是PFOS引起神经毒性的机制之一。

Effects of perfluorooctane sulfonate on Glu, PKC and PKA activities in mouse brain

OBJECTIVE: To study the effects of perfluorooctane sulfonate (PFOS) on contents of glutamate and activity of protein kinase C (PKC) and A (PKA) and ultrastructure injury in the brain of male mice and to explore the mechanism of neurotoxicity and patho-alteration resulted from PFOS. METHODS: 44 male mice were randomly divided into four groups, who were respectively orally given 0, 5, 10, 20 mg/kg PFOS for 10 days. The Glu concents in the brain of the mice was measured with spectrophotometer and protein kinaes activity were measured with non-radioactive assay of protein kinase and the changes of cerebral cortex ultrastructure were observed. RESULTS: Contents of Glu in 10 and 20 mg/kg groups were (1.57 +/- 0.11) and (1.62 +/- 0.16) mmol/g prot respectively,which was significantly increased compared with the corresponding controlled group (1.45 +/- 0.13) mmol/g prot] (F = 39.59, P < 0.05). PKC activity in 5, 10 and 20 mg/kg BW groups were (29.05 +/- 2.89), (33.65 +/- 3.82) and (34.20 +/- 3.16) pmol x min(-1) x (mg prot)-1 respectively, which was significantly increased compared with the corresponding control group (24.53 +/- 2.88) pmol x min(-1) x (mg prot)-1] (F = 7.75, P < 0.05). Compared with the corresponding control group, PKA in 5, 10 and 20 mg/kg BW groups increased by (24.12 +/- 3.86)%, (34.02 +/- 3.04)% and (33.42 +/- 3.71)% with a statistical significance (F = 26.27, P < 0.01). The exposed mice had cerebral cortex ultrasrtucture injury of cell nucleus envelope hollow. CONCLUSION: Exposure to PFOS increases Glu contents and activity of PKC and PKA in mouse brain and induce the cerebral cortex ultrastructral injury, a possible mechanism of the neurotoxicity caused by PFOS.