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目的研究苯并[a]芘(B[a]P)亚慢性染毒致大鼠学习记忆功能损伤及Tau蛋白磷酸化的改变。方法 50只无特定病原体级雄性SD大鼠随机分为空白对照组、溶剂对照组和低、中、高剂量染毒组,3个剂量染毒组分别给予1.00、2.50、6.25 mg/kg体质量的B[a]P(橄榄油溶解),溶剂对照组给予1 ml/kg体质量橄榄油,腹腔注射隔日染毒12周。空白对照组不采取处理措施。Morris水迷宫检测大鼠神经行为功能,免疫印迹法检测大鼠脑组织Tau、Tau-Thr181、Tau-Ser199、Tau-Thr231和Tau-Ser396蛋白相对表达水平。结果 5组间逃避潜伏期差异有统计学意义(P<0.05),组间与染毒后观察时间有交互作用(P<0.05)。中、高剂量染毒组目标象限停留时间、穿越平台次数均低于溶剂对照组(P<0.05,P<0.01),高剂量染毒组第1次穿越平台时间高于溶剂对照组(P<0.05)。中、高剂量染毒组Tau、Tau-Thr181、Tau-Ser199、Tau-Thr231蛋白相对表达水平分别高于溶剂对照组和低剂量染毒组(P<0.01,P<0.05);高剂量染毒组Tau-Thr181、Tau-Ser199及Tau-Thr231蛋白相对表达水平分别高于中剂量染毒组(P≤0.05);5组组间Tau-Ser396蛋白相对表达水平比较,差异无统计学意义(P>0.05)。Tau蛋白总磷酸化水平与目标象限停留时间和穿越平台次数呈负相关[相关系数(r)=-0.74,P<0.01;r=-0.80,P<0.01],与第5天逃避潜伏期和第1次穿越平台时间呈正相关[Spearman相关系数(rS)=0.72,P<0.01;rS=0.83,P<0.01)。结论 B[a]P亚慢性暴露可致大鼠学习记忆能力损伤及Tau蛋白磷酸化改变。
Objective To investigate the changes of learning and memory impairment and phosphorylation of Tau induced by subchronic exposure to benzo [a] pyrene (B [a] P) in rats. Methods Fifty male Sprague Dawley rats without specific pathogen were randomly divided into blank control group, solvent control group and low, medium and high dose exposure groups. The three dose exposure groups were given 1.00, 2.50 and 6. 25 mg / kg body weight respectively Of B [a] P (olive oil dissolved), solvent control group was given 1 ml / kg of body weight olive oil, intraperitoneal injection for 12 weeks every other day. Blank control group did not take measures. The neurobehavioral function of rats was detected by Morris water maze, and the relative expression of Tau, Tau-Thr181, Tau-Ser199, Tau-Thr231 and Tau-Ser396 protein in rat brain were detected by Western blotting. Results The differences of escape latency between the five groups were statistically significant (P <0.05). Interaction between the two groups was observed after the exposure (P <0.05). The target quadrant dwell time and the number of crossing the platform of medium and high dose exposure groups were lower than that of the solvent control group (P <0.05, P <0.01), and that of the high dose exposure group was higher than that of the solvent control group (P < 0.05). The relative expression levels of Tau, Tau-Thr181, Tau-Ser199 and Tau-Thr231 in medium and high dose groups were higher than that in solvent control group and low dose group (P <0.01, P <0.05) The relative expression levels of Tau-Thr181, Tau-Ser199 and Tau-Thr231 were higher than those of the middle-dose group (P≤0.05). There was no significant difference in the relative expression levels of Tau-Ser396 between the 5 groups > 0.05). The total phosphorylation level of Tau was negatively correlated with the target quadrant dwell time and the number of crossing platforms [r = -0.74, P <0.01; r = -0.80, P <0.01] One time pass through the platform was positively correlated [Spearman’s correlation coefficient (rS) = 0.72, P <0.01; rS = 0.83, P <0.01). Conclusion Subchronic exposure of B [a] P can cause impaired learning and memory ability and phosphorylation of Tau in rats.