脑啡肽酶抑制剂:开辟治疗糖尿病心血管和肾脏并发症新天地?  

Enkephalin Inhibitor: New World of Cardiovascular and Renal Complications of Diabetes?

作　　者：潘紫曜 李琳琳 李昌祁[2] PAN Zi-yao;LI Lin-lin;LI Chang-qi(Daqing Longnan Hospital Pharmacy, Daqing Heilongjiang 163458, China;Department of Endocrinology of Daqing Longnan Hospital, Daqing Diabetes Clinic Center, Heilongjiang Daqing 163458, China)

机构地区：[1]大庆龙南医院药剂科,黑龙江大庆163458 [2]大庆龙南医院内分泌科大庆市糖尿病诊疗中心,黑龙江大庆163458

出　　处：《药品评价》2017年第17期9-14,共6页Drug Evaluation

摘　　要：糖尿病发病率不断攀升,是二十一世纪全球公共卫生面临的重大威胁。近年来,除了胰岛素和各种口服降糖药外,随着不同治疗靶点的降糖药物不断涌现,给糖尿病治疗带来更多的选择。阻断肾素-血管紧张素系统(RAS)是药物治疗糖尿病心血管疾病(CVD)和慢性肾脏病(CKD)的关键,这些伴发症也是糖尿病患者致残和死亡的主要原因。抑制脑啡肽酶(NEP)可以使利钠肽生物利用度的增加,同时辅助抑制肾素-血管紧张素系统(RAS),有利于改善肾脏血液循环。奥马曲拉,是第一个具有双重抑制作用的药物,同时抑制血管紧张素转化酶(ACE)和脑啡肽酶(NEP)。据报道,相比ACEI类药物,在糖尿病动物模型实验中,表现出优越的抗高血压、抗动脉粥样硬化、胰岛素增敏以及心血管和肾脏的双重保护作用。但是在高血压患者的临床试验中,奥帕曲拉增加血管性水肿等严重不良反应,使得它作为抗高血压药物受到阻碍。这一事件促使了血管紧张素受体和脑啡肽酶双重抑制剂(ARNi)的发展。第一个ARNi的代表,LCZ696(沙库必曲/缬沙坦),能够阻止心血管和肾功能的衰退,因此具有抗CKD和CVD的作用。最近,LCZ696被FDA批准用于治疗心脏衰竭。这里简单回顾并总结,关于脑啡肽酶抑制剂(NEPi)用于治疗糖尿病引起的CVD和CKD。Diabetes is an enormous and ever-growing calamity and a global public health threat of the21st century.Besides insulin and oralhypoglycaemic drugs,blockage of the renin-angiotensin system(RAS)denotes a key pharmacotherapy for the management of cardiovascular(CVD)and chronic kidney diseases(CKD),which are the leading causes of disability and death among diabetic patients.Neprilysin(NEP)inhibition,auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system.Omapatrilat,a dual angiotensinconvertingenzyme(ACE)and NEP inhibitor has been reported to show superior anti-hypertensive,anti-atherosclerotic,insulin-sensitizing,cardiovascular and renoprotective effects to ACE inhibitors in experimental animal models for diabetes.Clinical trials showed omapatrilat increasedthe risk of angioedema on hypertensive subjects,thus the development as anti-hypertensive drug was hampered.This event prompted the developmentofangiotensin receptor neprilysin inhibitors(ARNi).The first representative of ARNi,LCZ696(Sacubitril/Valsartan)halted cardiovascular and renalfunctional decline and hence protected against CKD and CVD.Recently,LCZ696was approved by U.S.Food and Drug Administration for thetreatment of heart failure.This concise review intends to summarize the currently available reports on NEPi as a therapeutic intervention to treat CVDand CKD associated with diabetes.

关 键 词：脑啡肽酶抑制剂 NEPi ARNi CKD CVD 

分 类 号：R587.2[医药卫生—内分泌]