金匮肾气丸和六味地黄丸对小鼠脑海马核团蛋白质组学作用的比较研究

Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills

作为补肾阳和补肾阴的金匮肾气丸和六味地黄丸对于脑功能的影响渐为关注,但是对其所调控的蛋白表达的差异性尚有待探讨。为此,作者对两药在小鼠脑海马蛋白质组学表达的差异性进行了研究。给正常小鼠灌胃金匮肾气丸和六味地黄丸7 d,取小鼠脑海马,LC-MS/MS定量检测蛋白质,结果显示,在所测5 860个有效蛋白中,金匮肾气丸单独作用的蛋白有151个,六味地黄丸单独作用的蛋白有282个,两者同时有作用的蛋白共75个。金匮肾气丸上调蛋白表达多于下调蛋白,其表达上调蛋白与下调蛋白比为1.627;六味地黄丸则上调蛋白表达明显少于下调蛋白,表达上调蛋白与下调蛋白比为0.56。金匮肾气丸表达上调蛋白主要涉及膜转运、突触囊泡周期、5-羟色胺能突触、多巴胺能突触等,提示其对神经系统及其递质转运具有潜在的促进作用;六味地黄丸下调蛋白主要涉及膜转运、突触、离子转运(钾钠转运)、神经递质转运、固有免疫和获得性免疫应答、补体激活、炎症应答等,其中对于solute carrier(SLC)超家族表现出明显的下调作用,提示其对于膜兴奋及其转运具有潜在的抑制作用。最后,在对于正常小鼠及其皮质酮模型小鼠脑海马相关基因表达验证也显示出一致的结果。该研究对于从蛋白质调控网络上认识金匮肾气丸和六味地黄丸作用于脑功能提供了实验依据。

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention,while the differences of protein expression regulated by Jingui and Liuwei remain to be studied.This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days.The protein expression was quantified using LC-MS/MS.The results showed that among the 5 860 proteins tested,151,282 and 75 proteins responded to Jingui alone,Liuwei alone,and both drugs,respectively.The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group.The proteins up-regulated by Jingui were mainly involved in membrane transport,synaptic vesicle cycle,serotonergic synapse,dopaminergic synapse and so on,suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system.The proteins down-regulated by Liuwei were mainly involved in membrane transport,synapse,ion transport(potassium and sodium transport),neurotransmitter transport,innate and acquired immune responses,complement activation,inflammatory response,etc.In particular,Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily,which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport.Finally,consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior.This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.