氯化铝染毒大鼠海马组织NMDAR-ERK通路调节H3K9ac、H3K9me2、HP1和BDNF蛋白的表达

Expression of H3K9ac,H3K9me2,HP1,and BDNF Mediated by NMDAR-ERK Pathway in Hippocampus Tissues of Rats Exposed to Aluminum Chloride

[目的]研究慢性染铝对大鼠海马组织N-甲基-D-天冬氨酸受体(NMDAR)、p-细胞外信号调节蛋白激酶(p-ERK)、H3K9ac、H3K9me2、HP1、BDNF表达量的影响。[方法]雄性SD大鼠,SPF级,共24只,按体重随机分为对照组(自来水)和铝染毒2、12、72 mg/kg组,每组6只。染毒组每天经饮水染毒Al Cl3,共持续120 d。染毒结束后,用Western blot法测定各种蛋白表达量。[结果]与对照组相比,72 mg/kg组海马中NMDAR、p-ERK的表达量均降低(P<0.05);72 mg/kg组H3K9ac、BDNF的表达量与对照组比较均下降(均P<0.01),且随着染毒剂量的增加表达量均呈下降趋势(rNMDAR=-0.61;rp-ERK=-0.69;rH3K9ac=-0.93;rBDNF=-0.73,均P<0.05);而72 mg/kg组H3K9me2、HP1的蛋白表达量均高于对照组(P<0.05,P<0.01),且随着染毒剂量的增加表达量呈上升趋势(rH3K9me2=0.67;rHP1=0.72,均P<0.01)。[结论]铝可能经NMDAR-ERK通路引起大鼠海马组织H3K9ac、H3K9me2、HP1、BDNF表达量发生改变。

[ Objective ]To examine expression levels of N-methyl-D-aspartate receptor （NMDAR）, phosphorylated- extracellular signal regulated protein kinase （p-ERK）, H3K9ac, H3K9me2, HP1, and BDNF in hippocampus tissue of rats chronically exposed to aluminum. [ Methods ] Twenty-four male SD rats （specific pathogen free） were randomly selected by body weight into four groups, in which drinking water contained 0, 2, 12, and 72mg/kg of aluminum chloride （AlCl_3） for 120d respectively. The protein expression levels of NMDAR, pERK, H3K9ac, H3K9me2, HP1, and BDNF were detected by Western blot. [ Results ] Compared with the control group, the expression levels of NMDAR, pERK, H3K9ac, and BDNF in hippocampus of the 72 mg/kg aluminum exposed group were significantly lower （P 〈 0.05 or P〈 0.01） in an inverse dose-dependent manner （r_NMVAR=-0.61, r_pEsr=-0.69, r_H3K9se=--0.93, and r_SDNF=--0.73, all PS 〈 0.05）. However, the expression levels of H3K9me2 and HP1 in hippocampus of the 72 mg/kg aluminum exposed group were both significantly higher （P 〈 0.05） in a dose-dependent manner （r_H3Kg2=0.67 and r_Hp1=0.72, both Ps〈0.01）. [ Conclusion ] Chronic aluminum exposure may change the expression of H3K9ac, H3K9me2, HP1, and BDNF via NMDAR-ERK pathway.