目的探讨铝染毒对大鼠海马PHF8、H3K9me2、脑源性神经营养因子(BDNF)表达的变化以及对海马长时程增强(LTP)幅值改变的调节作用。方法雄性SD大鼠,共40只,按体重随机分为对照组、2、12、72mg/kg染毒剂量组,每组10只,对照组为自来水,染毒组的染毒剂量分别为2、12、72mg/kg。每天经饮水染毒,共持续90d。染毒结束后,用电生理学方法检测大鼠海马LTP,免疫印迹(westem-blot)方法测定PHF8、H3K9me2、BDNF的表达量。结果电生理实验结果显示,与对照组比较,各染毒组在不同时点的平均fEPsP振幅明显下降,差异有统计学意义(P〈0.01)。与对照组比较,各染毒组PHF8的表达量下降,差异有统计学意义(P〈0.01);与对照组和2m/kg剂量组比较,72mg,kg剂量组H3K9me2表达量上升,差异有统计学意义(P〈0.05)。与对照组比较,12、72mg/妇剂量组BDNF表达量降低,差异有统计学意义(P〈0.05)。结论铝染毒可能通过作用于大鼠海马PHF8-H3K9me2-BDNF途径因子,对LTP产生用影响,继而损伤大鼠的学习记忆能力。
Objective In this research, we have observed changes of PHF8, H3K9me2,BDNF, and their regulatory roles in changing the amplitude value of LTP in hippocampus due to aluminum exposure so that we can discuss the impact on the learning and memory that caused by chronic aluminum exposure. Methods Forty healthy SPF grade SD male rats were randomly divided into four groups by weight, including control group and low, medium, high dose aluminum exposed group, each group had 10 rats. The exposed rats drank water containing different doses of aluminum chloride (A1CI3) (2,12,72 mg/kg AI^3+) for 90 d. We measured LTP in hippocampus by electrophysiological grapier and detected the expression of PHF8 ,H3K9me2 ,BDNF by western- blot. Results Electrophysiological measurements shows that compared with that of control group, the average of fEPSPs was decreased at different time points in all exposed groups (P〈0.01). The results of western-boh test demonstrated that the expression of PHF8 in the exposed groups were significantly lower than those of control group (P〈0.O1). And the expression the of H3K9me2 of medium and high dose groups were significantly higher than control group (P〈0.05). While the expression of BDNF of medium and high dose groups were decreased compared with the control group (P〈0.05). Conclusion Chronic aluminum exposure can reduce the LTP via the route of PHF8-H3K9me2-BDNF in the hippocampus of rats, which then may impair the ability of learning and memory.