替普瑞酮对亚慢性苯并[a]芘染毒大鼠神经行为改变的保护作用

Protective effect of teprenone on neurobehavioral damage in rats with subchronic benzo[a]pyrene exposure

[背景]苯并[a]芘(BaP)具有神经毒性,可导致暴露人群和动物神经行为异常。替普瑞酮具有神经保护作用,但其是否可以防治BaP诱发的神经毒作用尚不清楚。[目的]观察替普瑞酮对亚慢性染毒BaP大鼠学习记忆能力的影响,探讨替普瑞酮对BaP神经行为损伤的保护作用,为BaP神经毒作用的防控提供依据。[方法]选择40只健康雄性SD大鼠,体重为180~200 g,随机分为溶剂(橄榄油)对照组、替普瑞酮组、BaP染毒组和替普瑞酮+BaP染毒组,每组10只,按800 mg·kg^(-1)(以体重计)剂量灌胃替普瑞酮,腹腔注射染毒6.25 mg·kg^(-1) BaP,隔日染毒,持续90 d。采用Morris水迷宫进行神经行为学测试,石蜡切片后通过HE染色观察海马组织病理学改变,采用TUNEL法及Annexin V-FITC/PI双染法检测海马组织神经细胞凋亡率,采用Western blotting法检测大鼠海马组织热休克蛋白70(Hsp70)的表达水平。[结果]染毒后替普瑞酮+BaP染毒组体重[(311.10±22.38)g]增长大于BaP染毒组[(283.42±33.95)g](P<0.05)。Morris水迷宫结果显示替普瑞酮+Ba P染毒组寻找平台的平均逃避潜伏期[(29.17±1.90)s]和平均总路程[(132.51±1.96)cm]低于BaP染毒组[(46.77±2.14)s、(181.97±2.09)cm](P<0.05)。BaP染毒组海马区神经细胞结构破坏,数量减少,排列凌乱,替普瑞酮+BaP染毒组比BaP染毒组损伤明显减轻。替普瑞酮+BaP染毒组大鼠海马神经细胞凋亡率[(7.73±5.16)%]低于BaP染毒组[(53.10±7.34)%],Hsp70蛋白表达水平(0.89±0.09)高于BaP染毒组(0.49±0.10)(P<0.05)。[结论]替普瑞酮可改善BaP染毒引起的大鼠神经行为的损伤,可能与其降低神经细胞凋亡率有关。

[Background]Benzo[a]pyrene(BaP)is neurotoxic and can cause neurobehavioral abnormalities in exposed humans and animals.Teprenone has neuroprotective effects,but whether it can prevent or antagonize BaP-induced neurotoxicity remains unclear.[Objective]This experiment observes the effect of teprenone on the learning and memory ability of subchronically BaP exposed rats,and explores the protective effect of teprenone on BaPinduced neurobehavioral damage,aiming to provide a basis for the prevention and control of BaP neurotoxic effects.[Methods]Forty healthy male SD rats weighing 180-200 g were randomly divided into a solvent(olive oil)control group,a teprenone group,a BaP group,and a teprenone+BaP group,with 10 rats in each group.Every other day,teprenone was intragastrically administered at a dose of 800 mg·kg^(-1)(by body weight),and BaP at 6.25 mg·kg^(-1) was given by intraperitoneal injection,for 90 d in total.The neurobehavior was tested by the Morris water maze.After paraffin sectioning and HE staining,the histopathological changes of hippocampus were observed.The apoptosis rate of hippocampal nerve cells was determined by TUNEL and Annexin V-FITC/PI double staining.The expression level of heat shock protein 70(Hsp70)was detected by Western blotting.[Results]The weight gain of the teprenone+BaP group[(311.10±22.38)g]was greater than that of the BaP group[(283.42±33.95)g](P<0.05).The Morris water maze results showed that the average escape latency[(29.17±1.90)s]and the average total distance[(132.51±1.96)cm]of the teprenone+BaP group were lower than that of the BaP group[(46.77±2.14)s and(181.97±2.09)cm](P<0.05)respectively.The BaP group showed nerve cell destruction,loss of neurons,and disorderly arrangement in hippocampus;in contrast,the above damage of the teprenone+BaP group was much alleviated than that of the BaP group.The apoptosis rate of hippocampal neurons of the teprenone+BaP group[(7.73±5.16)%]was lower than that of the BaP group[(53.10±7.34)%],and the expression level of Hsp70 protein of the teprenone+BaP group(0.89±0.09)was higher than that of the BaP group(0.49±0.10)(P<0.05).[Conclusion]Teprenone can ameliorate the neurobehavioral damage of rats induced by BaP exposure,which may be related to its function of decreasing neuronal apoptosis.