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目的研究苯并[a]芘亚慢性染毒对大鼠学习记忆及蛋白激酶C(PKC)、N-甲基-D-天冬氨酸受体(NMDAR)、钙调蛋白激酶Ⅱ(Ca MKⅡ)的影响。方法无特定病原体级健康雄性SD大鼠50只随机分为空白对照组、溶剂对照组和低、中、高剂量组,每组10只。空白对照组不作任何处理,后4组分别予剂量为0.00、1.00、2.50和6.25 mg/kg体质量的苯并[a]芘橄榄油溶液,隔日腹腔注射染毒60 d后,采用Morris水迷宫实验检测大鼠学习记忆能力,免疫印迹法检测大鼠海马组织中PKC、NMDAR和Ca MKⅡ蛋白相对表达水平。结果 Morris水迷宫实验结果显示:大鼠逃避潜伏期在染毒剂量与染毒时间存在交互作用(P<0.01)。中剂量组大鼠第1次穿越平台时间分别高于空白对照组、溶剂对照组和低剂量组(P<0.05),而目标象限停留时间低于空白对照组(P<0.05);高剂量组大鼠第1次穿越平台时间分别高于其余4组(P<0.05),目标象限停留时间分别低于空白对照组、溶剂对照组和低剂量组(P<0.05)。低、中剂量组NMDAR和Ca MKⅡ蛋白相对表达水平分别低于空白对照组(P<0.05);高剂量组PKC和Ca MKⅡ蛋白的相对表达水平均分别低于其余4组(P<0.05),NMDAR蛋白的相对表达水平分别低于空白对照组、溶剂对照组和低剂量组(P<0.05)。结论苯并[a]芘亚慢性染毒所致大鼠学习记忆功能损伤可能与PKC、NMDAR及Ca MKⅡ的表达下调,进而影响突触可塑性有关。
Objective To investigate the effects of sub-chronic exposure to benzo [a] pyrene on learning and memory, expression of protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDAR), calmodulin kinase Ⅱ )Impact. Methods Fifty healthy male SD rats without specific pathogen were randomly divided into blank control group, solvent control group and low, medium and high dose groups of 10 rats. The blank control group was given no treatment. After four groups were given benzo [a] pyrene olive oil with the dosage of 0.00, 1.00, 2.50 and 6.25 mg / kg body weight respectively, and the other day after the intraperitoneal injection for 60 days, The learning and memory abilities of rats were detected by experiments. The relative expression levels of PKC, NMDAR and Ca MKII in hippocampus were detected by Western blotting. Results Morris water maze test results showed that there was interaction between exposure dose and exposure time (P <0.01). The mean transit time of rats in the middle-dose group was higher than that in the blank control group, the solvent control group and the low-dose group (P <0.05), while the target quadrant stay time was lower than that in the blank control group (P <0.05) Rats in the first pass through the platform time were higher than the other four groups (P <0.05), the target quadrant retention time was lower than the blank control group, solvent control group and low-dose group (P <0.05). The relative expression levels of NMDAR and Ca MKII in low and middle dose groups were lower than those in blank control group (P <0.05), while the relative expression levels of PKC and Ca MKII in high dose group were lower than those in the other 4 groups (P <0.05) The relative expression levels of NMDAR protein were lower than the blank control group, solvent control group and low-dose group (P <0.05). Conclusions The impairment of learning and memory in rats induced by sub-chronic exposure to benzo [a] pyrene may be related to the down-regulation of PKC, NMDAR and Ca MKII, which may affect the synaptic plasticity.