【摘要】 目的观察胚胎期和生长期连续砷暴露的仔鼠脑神经细胞线粒体功能和超微结构的变化,探讨砷对子代大鼠脑功能损伤机制。方法 SD大鼠随机分成对照组、低、高砷染毒组,染砷组自由饮用As2O3水溶液,剂量为0.6、15 mg/kg,6周后,各组分别雄雌2∶1合笼产仔,仔鼠由各自染砷母代乳养至断乳后,仔鼠离开母鼠继续本组剂量染砷到6和16周,测定仔鼠脑神经细胞线粒体的呼吸活性和ATP合成量,同时观察线粒体的超微结构变化。结果断乳后继续染砷6和16周的高、低剂量组仔鼠脑细胞线粒体Ⅲ态呼吸(R3)比对照组明显降低,以高剂量组仔鼠最为显著(P<0.01);呼吸控制率(RCR)在各染砷组都有所降低,但以16周高剂量组仔鼠降低更显著(P<0.05)。染砷组的ATP合成量比对照组明显减少,以高砷组仔鼠减少更显著(P<0.01);电镜下染砷组线粒体有基质肿胀,部分嵴减少甚至断裂,高砷组仔鼠还见线粒体外膜断裂,部分线粒体呈空泡样改变,有的甚至溶解。结论仔鼠在胚胎期与生长发育期连续砷暴露其脑神经细胞线粒体呼吸功能和能量代谢功能均会受到明显损伤,损伤程度有剂量和时间-效应关系。更多还原

【Abstract】 Objective To investigate the toxic effects of arsenic on brain nerve cellular mitochondrial function and ultrastructure of F1 generation rats exposed to arsenic during gestation and growth.Methods Sprague-Dawley(SD) rats of cleanliness grade were randomly divided into three group(low-,high-dose arsenic group and control group),treated with arsenic(As2O3) at doses of 10 mg/kg,0.4 mg/kg,the control group with distilled water,for 6 consecutive weeks.F1 pup rats were lactated by dam exposed arsenic until weaning,F1 pup rats continuously exposed to arsenic for 6 and 16 weeks after weaning respectively.The respiratory activity and ATP amounts of brain cellular mitochondria were determined in all groups and mitochondria ultrastructure changes were observed.Results In F1 pup rats of low-and high-arsenic continued exposed arsenic for 6 and 16 weeks after weaning,the Ⅲ condition respiration rates(R3) of brain cellular mitochondria were obviously lower than that in the control group,and the high-dose group were more lower compared with low-dose group.The respiratory control ratio(RCR)in high-dose arsenic exposed for 16 weeks were more degraded than that of arsenic exposed group.ATP amounts of brain cellular mitochondria of arsenic exposed group decreased compared with that in the control group(P<0.01),and high-dose group more striking decreased.The ultrastructures of brain cells mitochondrion were investigated under electron microscope,mitochondria showed ground substance tumescence,lophos decrease and breakage,even adventitia breakage,vacuolus changed and dissolved in high-dose group were observed. Conclusion Arsenic may induce brain nerve cells mitochondrial respiratory and energy metabolism function damaged in F1 pup rats consecutively exposed to arsenic from gestation to growth period,the degree of injury is positively relative to exposure dose and time.更多还原