【摘要】 目的通过复制成年动物铅暴露模型,研究铅暴露时间长短对大脑皮质自噬蛋白ATG5、Beclin1、LC3B表达的变化。方法选取18只豚鼠随机分为4组:对照组(3只),以及铅暴露15、60和90 d组(每组5只)。用0.2%醋酸铅饮用水复制动物铅暴露模型,对照组给予等量的生理盐水喂养;免疫组织化学法检测ATG5、Beclin1和LC3B的表达。结果与对照组相比,不同时间铅暴露组自噬蛋白ATG5、Beclin1和LC3B的阳性表达升高(P<0.05)。铅暴露90 d组的ATG5表达水平与各暴露组比较,差异有统计学意义(P<0.05)。铅暴露15 d组与60 d组的ATG5表达水平比较,差异无统计学意义(P>0.05)。各暴露组Beclin1和LC3B蛋白水平比较,差异无统计学意义(P>0.05)。结论环境铅饮用水可通过自噬蛋白ATG5、Beclin1及LC3B引起大脑皮质区的自噬反应,推测铅暴露激活的早期自噬反应可能对大脑皮质发挥神经毒性作用,对成年豚鼠大脑造成不可逆转的损害。更多还原

【Abstract】 Objective To study the effect of lead exposure time on expressions of autophagy proteins including ATG5, Beclin1 and LC3B in the cerebral cortex by establishing the lead exposure model in adult guinea pigs. Methods Eighteen guinea pigs were randomly divided into 4 groups, with 3 in the control group(without lead exposure) and 5 in each of the 3 lead exposure groups with exposure to lead for 15, 60 and 90 days. The model was established using 0.2% lead acetate drinking water, and the control group was given the same amount of normal saline. The expression levels of ATG5, Beclin1 and LC3B proteins were detected by immunohistochemistry. ResultsCompared with the control group, the positive expressions of ATG5, Beclin1 and LC3B were significantly increased in the 15-day, 60-day and 90-day lead exposure groups(P < 0.05). The expression level of ATG5 in the 90-day lead exposure group was significantly higher than those of other lead exposure groups(P < 0.05). No significant difference was observed in the expression level of ATG5 between the 15-day and 60-day lead exposure groups(P > 0.05).And there was no significant difference in the expression level of Beclin1 or LC3B among the lead exposure groups(P > 0.05). Conclusions Lead drinking water can cause autophagy in the cerebral cortex through the autophagy proteins ATG5, Beclin1 and LC3B. It is speculated that the early autophagic response induced by lead exposure may exert neurotoxic effect on cerebral cortex and cause irreversible damage in adult guinea pigs.更多还原