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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 investigate the effect of perfluorooctane sulfonate (PFOS) on glutamate, protein kinase C (PKC) and protein kinase A (PKA) activity in brain and the ultrastructure of PKOS in male mice, Toxicity mechanism. Methods Forty-four male Kunming mice were divided into 4 groups according to body weight, 11 in each group. The doses of PFOS were 5, 10, and 20 mg / kg, respectively. The control group was given the same volume of 2% Tween-80 and the rats were orally exposed for 10 days. The contents of glutamate in brain of mice were determined by spectrophotometer. The activity of PKC and PKA were measured by non-radioactive protein kinase assay. The ultrastructure of cerebral cortex was observed by transmission electron microscope. Results Compared with control group [(1.45 ± 0.13) mmol / g protein], the contents of glutamate in the brain of mice exposed to 10 and 20 mg / kg were (1.57 ± 0.11) and (1.62 ± 0.16) mmol / (29.05 ± 2.89), (33.65 ± 3.82) and (34.20 ± 3.16) pmol, respectively, compared with the control group (F = 39.59, P <0.05) · Min ~ (-1) · (mg protein) ~ (-1), compared with the control group [(24.53 ± 2.88) pmol · min -1 (mg protein) -1) Statistical significance (F = 7.75, P <0.05). Compared with the control group, the PKA activities in the 5, 10 and 20 mg / kg groups increased by (24.12 ± 3.86)%, (34.02 ± 3.04)% and (33.42 ± 3.71)%, respectively, with significant difference = 26.27, P <0.01). However, the trend of increasing PKC and PKA activity slowed down when PFOS dose was 20 mg / kg. Administration of mouse PFOS can cause ultrastructural damage in the nucleus of the cerebral cortex cells. Conclusions Exposure of PFOS to murine cerebrospinal fluid can increase glutamate, PKC and PKA activity and cause ultrastructural damage to cerebral cortical cells, which may be one of the mechanisms of PFOS neurotoxicity.