从心肾表观遗传修饰探讨交泰丸干预失眠动物模型的作用机制研究  

Mechanism of Jiaotai pill in intervention of insomnia animal model from epigenetic modificationsof heart and kidney

作　　者：赵俊云[1] 杨晓敏[1] 胡秀华[1] 曹䶮 简郭血骄 杨向竹[1] 郭健[1] ZHAO Jun-yun;YANG Xiao-min;HU Xiu-hua;CAO Yan;JIANGUO Xue-jiao;YANG Xiang-zhu;GUO Jian(Beijing University of Chinese Medicine,Beijing 100029)

机构地区：[1]北京中医药大学,北京100029

出　　处：《世界中西医结合杂志》2020年第6期1064-1066,1079,共4页World Journal of Integrated Traditional and Western Medicine

基　　金：中央高校基本科研业务费专项资金资助(2017JYBJS151);北京中医药大学横向课题(2170071720009)。

摘　　要：目的从心脏和肾脏DNA甲基化和组蛋白乙酰化修饰探讨交泰丸干预失眠动物模型的机制。方法48只雄性SD大鼠随机分为正常组、模型组和交泰丸组,每组16只。实验第1天,模型组和交泰丸组按300 mg/kg一次性腹腔注射氯苯丙氨酸(PCPA)建立失眠模型,正常组一次性腹腔注射等体积生理盐水。实验第3天,交泰丸组灌胃交泰丸水提液5 g/kg,1次/d,连续3 d,正常组和模型组灌胃等体积生理盐水。ELISA法检测心脏和肾脏表观遗传修饰主要酶DNA甲基转移酶1(DNMT1)、组蛋白去乙酰化酶(HDAC)活性及乙酰化组蛋白H3(Acetyl-Histone H3)水平,比色法检测心脏和肾脏DNA甲基化水平。结果PCPA致失眠大鼠心脏DNMT1、HDAC活性、DNA甲基化水平显著上升,肾脏DNMT1活性、HDAC活性、DNA甲基化水平显著下降,心脏Acetyl-Histone H3水平显著下降,肾脏Acetyl-Histone H3水平显著上升。交泰丸干预可显著降低失眠大鼠心脏DNMT1、HDAC活性和DNA甲基化水平,显著上调肾脏DNMT1活性和DNA甲基化水平,显著下调肾脏Acetyl-Histone H3水平。结论交泰丸干预可调节失眠大鼠心脏和肾脏的DNA甲基化和组蛋白乙酰化修饰水平,从表观遗传学角度看,心肾不交可能与心脏的DNA甲基化、组蛋白去乙酰化以及肾脏的DNA去甲基化、组蛋白乙酰化的两极发展有关。Objective To explore the mechanism of Jiaotai Pill intervention in animal model of insomnia from DNA methylation and histone acetylation of heart and kidney.Methods 48 male SD rats were randomly divided into normal group,model group and Jiaotai pill group,16 rats in each group.On the first day of the experiment,the model group and Jiaotai pill group were injected with chlorophenylalanine(PCPA)intraperitoneally at 300 mg/kg.The normal group was injected intraperitoneally with equal volume of normal saline.On the third day of the experiment,the Jiaotai pill group was gavaged with Jiaotai pill water extract 5 g/kg,once per day for 3 consecutive days.The normal group and model group were gavaged with equal volume of normal saline.ELISA method was used to detect the activities of DNA methyltransferase 1(DNMT1),histone deacetylase(HDAC),and the level of acetylated histone H3(Acetyl-Histone H3).Heart and kidney DNA methylation levels.Were detected by colorimetnc method.Results The activity of DNMT1 and the level of Acetyl-Histone H3 in heart increased significantly in PCPA-induced insomnia rats compared to normal group.The activity of DNMT1 and HDAC in kidney decreased significantly.The level of Acetyl-Histone H3 decreased in heart while increased in kidney.DNA methylation level increased in heart while decreased in kidney.Jiaotai Pill intervention significantly reduced the activity of DNMT1 and HDAC and the level of Acetyl-Histone H3 in hearts.And it upregulated DNMT1 activity and DNA methylation level while downregulated Acetyl-Histone H3 leve in kidneys.Conclusion Jiaotai pill intervention can regulate DNA methylation level and histone acetylation level.From the perspective of epigenetics,heart and kidney disharmony may be associated with DNA methylation and histone deacetylation in heart and DNA demethylation and histone acetylation in kidney.

关 键 词：失眠 交泰丸 表观遗传修饰 

分 类 号：R285.5[医药卫生—中药学]