假性缺氧驱动“衰老-癌变”的脾肾亏虚病机探讨  

Discussion on spleen and kidney deficiency pathogenesis of pseudohypoxia promoting 'senility-carcinogenesis'

作　　者：靖林林[1,2] 马晔 王浩 William K.K.Wu[3] 孙学刚 JING Lin-lin;MA Ye;WANG Hao;William K.K.Wu;SUN Xue-gang(School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China;TCM-Integrated Hospital of Southern Medical University,Guangzhou 510315,China;The Chinese University of Hong Kong,Hongkong 999077,China)

机构地区：[1]南方医科大学中医药学院,广州510515 [2]南方医科大学中西医结合医院,广州510315 [3]香港中文大学,香港999077

出　　处：《中华中医药杂志》2018年第11期4870-4873,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81573848;No.81774172);广东省自然科学基金项目(No.2014A030313323;No.2017A030313903);广东省科学技术厅-广东省中医药科学院联合科研项目(No.2014A020221011);广州市科技计划(No.201607010146);南方医科大学科研启动计划(No.CX2015N008)~~

摘　　要：脾肾亏虚是"衰老-癌变"进程主要的脏腑病机。衰老过程中衰老代谢物烟酰胺腺嘌呤二核苷酸(NAD+)的降低,肿瘤代谢物(R)-2羟戊二酸[(R)-2HG]、延胡索酸和琥珀酸的累积,体现肾不藏精,脾失健运。缺氧诱导因子1α(HIF-1α)在正常组织升高,诱导假性缺氧状态,是衰老代谢物与肿瘤代谢物的整合性枢纽,驱动氧化磷酸化向瓦博格样有氧糖酵解的转变。假性缺氧通过表观遗传修饰如组蛋白甲基化、组蛋白乙酰化和DNA甲基化,诱导循序渐进的代谢重编程导致脾肾相互滋生化源不足,产生易于肿瘤发生的微环境,产生肿瘤样状态。健脾补肾可能通过"卡路里限制样效应",改善能量代谢障碍,延缓或逆转衰老-癌变进程。Deficiency of Spleen and Kidney is the major zang-fu viscera pathogenesis of ＇senility-carcinogenesis＇ process. Decreased gerometabolites nicotinamide adenine dinucleotide（NAD＋）, and accumulation of oncometabolites（R）-2 hydroxyglutaric acid [（R）-2 HG], fumaric acid and succinic acid, reflecting that kidney cannot store essence andthe dysfunction of spleen in transportation. Hypoxia-inducible factor 1α（HIF-1α） is elevated in normal tissues and induces pseudohypoxia. It is an integrated hub of gerometabolites and oncometabolites, driving conversion of oxidative phosphorylation to wahlberg-like aerobic glycolysis. Pseudohypoxia induces progressive gradual metabolic reprogramming through epigenetic modifications such as histone methylation, histone acetylation, and DNA methylation, resulting in insufficient mutual breeding ofspleen and kidney, and resulting in a microenvironment that is prone to tumorigenesis to produce tumor-like state. Strictly adhere to the pathogenesis, invigorating spleen and tonifying kidney may improve the energy metabolism disorder and delay or reverse the senilitycarcinogenesis process through the ＇calorie restriction-like effect＇.

关 键 词：脾肾亏虚 衰老癌变 假性缺氧 衰老代谢物 肿瘤代谢物 表观遗传学 

分 类 号：R228[医药卫生—中医基础理论]