“异病同治”的生物学原理

Biological principles for"homotherapy for heteropathy"

人体多个系统的非感染性慢性疾病如糖尿病、非酒精性脂肪性肝病(NAFLD)、动脉粥样硬化(AS)、神经退行性疾病、骨质疏松和恶性肿瘤等具有一些共同的发病机制,如非可控性炎症(NRI)、肠道菌群紊乱、内质网应激、线粒体功能紊乱、哺乳动物雷帕霉素靶蛋白(mTOR)通路异常等,是临床“异病同治”的基础;一些临床常用的慢病治疗药物如二甲双胍、小檗碱、阿司匹林、他汀类和雷帕霉素,通过抗炎、调控肠道菌群、抑制内质网应激、改善线粒体功能、抑制mTOR等机制同时对多种慢性疾病具有改善作用,发挥“异病同治”的效果。而对于病毒性感染的疾病,因为有些病毒需要一些共性的病毒复制酶,这类酶的抑制剂也就成了临床抗病毒“异病同治”的运用范例(如同时抗艾滋病和乙肝的替诺福韦);尤其是在针对突发的病毒传染病时,这些病毒酶抑制剂在抗疫过程中快速地发挥出“异病同治”的重要作用,如阿兹夫定和索非布韦等。本文对“异病同治”的生物基础以及这些药物的可能作用机制的研究进展进行综述,以期为新药研发提供科学依据和新的参考。

Non-infectious chronic diseases in human including diabetes,non-alcoholic fatty liver disease(NAFLD),atherosclerosis(AS),neurodegenerative diseases,osteoporosis,as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation(NRI),gut microbiota dysfunction,endoplasmic reticulum stress,mitochondria dysfunction,and abnormality of the mammalian target of rapamycin(mTOR)pathway.These pathogenic mechanisms could be the basis for"homotherapy for heteropathy"in clinic.Some commonly used clinical drugs,such as metformin,berberine,aspirin,statins,and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of"homotherapy for heteropathy".The mechanisms of the above drugs may include anti-inflammation,modulation of gut microbiota,suppression of endoplasmic reticulum stress,improvement of mitochondria function,and inhibition of mTOR.For virus infectious diseases,as some viruses need certain commonly used replicases,the inhibitors of the replicases become examples of"homotherapy for heteropathy"for antiviral therapy in clinic(for example tenofovir for both AIDS and HBV infection).Especially,in case of outbreak of new emerging viruses,these viral enzyme inhibitors such as azvudine and sofibuvir,could be rapidly used in controlling viral epidemic or pandemic,based on the principle of"homotherapy for heteropathy".In this review article,we show the research progress of the biological basis for"homotherapy for heteropathy"and the possible mechanisms of some well-known drugs,in order to provide insights and new references for innovative drug R&D.