摘要
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 explore the effects of subchronic benzo[a]pyrene（ B[a]P） exposure on learning and memory ability,the expression of protein kinase C（ PKC）,N-methyl-D-aspartate receptor（ NMDAR）,and Calmodulin-dependent protein kinase Ⅱ（ Ca MKⅡ） in rats. Methods Fifty specific pathogen free healthy male SD rats were randomly divided into 5 groups： a blank control group,a solvent control group,a low-,a medium- and a high-dose groups,with 10 rats in each group. Blank control group was not treated; the other 4 groups were treated with 0. 00,1. 00,2. 50 and 6. 25 mg / kg body weight of B[a]P in olive oil respectively by intraperitoneal injection every other day for 60 days. Morris water maze test was used to evaluate the learning and memory ability of rats,the relative expression levels of PKC,NMDAR and Ca MKⅡwere detected by Western-blot. Results Morris water maze test showed that there were interactive effects between B[a]P exposure doses and exposure time on escape latency（ P〈0. 01）. The first time to go through the platform in medium-dose group was longer than those of the blank control group,solvent control group and low-dose group（ P〈0. 05）,while the time spent in the target quadrant was shorter than that of the blank control group（ P〈0. 05）; the first time to go through the platform was longer in the high-dose group compared with those of the rest 4 groups（ P〈0. 05）,while the time spent in the target quadrant was shorter than those of the blank control group,solvent control group and low-dose group（ P〈0. 05）.The relative expression levels of NMDAR and Ca MKⅡin low- and medium-dose groups were significantly lower than those in blank control group（ P〈0. 05）; the relative expression levels of PKC and Ca MKⅡin high-dose group were lower than those of the other 4 groups（ P〈0. 05）,the relative expression level of NMDAR of high-dose group was lower than those of the blank control group,solvent control group and low-dose group（ P〈0. 05）. Conclusion The damage of learning and memory ability in rats induced by subchronic B[a]P exposure may be related to the decreased expression of PKC,NMDAR and Ca MKⅡ,which could further influence the synaptic plasticity.
出处
《中国职业医学》
CAS
北大核心
2015年第5期505-509,共5页
China Occupational Medicine
基金
国家自然科学基金(81072279)
