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  

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

作　　者：王柯[1] 金一和[2] 于棋麟[1] 刘利[1] 赵翠霞[1] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理教研室,沈阳110001 [2]大连理工大学环境与生命学院生态毒理教研室

出　　处：《中华预防医学杂志》2007年第6期466-470,共5页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金(30471435)

摘　　要：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、20 mg/kg,对照组给予同等体积2%吐温-80,连续经口染毒10 d。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、20 mg/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、20 mg/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、20 mg/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20 mg/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。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 20mg/kg BW groups were （29. 05 ± 2. 89）, （ 33.65 ± 3.82） and （ 34. 20 ± 3.16 ） pmo] · min^-1· （mg prot）^-1 respectively, which was significantly increased compared with the corresponding control group [ （24. 53 ＋2. 88）pmol·min^-1· （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 ultrastructra] injury, a possible mechanism of the neurotoxicity caused by PFOS.

关 键 词：全氟辛烷磺酸 谷氨酸 蛋白激酶C 蛋白激酶A 

分 类 号：R114[医药卫生—卫生毒理学]