血管紧张素Ⅱ和胰岛素在心血管系统中的相互作用

摘要

Under normal physiology, insulin exerts vasodilatory and pro-survival actions via the phosphati dylinositol 3-kinase (PI3-kinase) pathway and vasoconstrictive and mitogenic actions via the mitogen-activated protein kinase (MAPK) pathway in the vasculature. In the insulin resistant states, insulin signals through the PI3-kinase pathway are blunted but its signals through the MAPK cascade remain intact. This imbalance predisposes insulin resistant patients to hypertension and atherosclerosis. The renin-angiotensin system (RAS) is expressed both systemically and locally in the cardiovascular system. Insulin resistance up-regulates the local RAS which contributes to the pathogenesis of hypertension, heart failure, and atherosclerosis. Angiotensin Ⅱ impairs insulin signaling, induces inflammation via the NF-κB pathway, reduces nitric oxide availability and facilitates vasoconstriction,leading to insulin resistance and endothelial dysfunction. Thus the RAS, insulin resistance and inflammation perpetuate each other and coordinately contribute to endothelial dysfunction, vascular injury and atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and mortality and the incidence of new onset Type 2 diabetes.%正常生理状态下,胰岛素不仅通过磷脂酰肌醇3-激酶(PI3K)途径产生血管舒张以及促生存作用,还通过有丝分裂原活化蛋白激酶(MAPK)途径在血管培养基上产生血管收缩及致有丝分裂作用.而在胰岛素抵抗状态下,通过PI3K途径转导的胰岛素信号变迟缓,但是通过MARK级联反应途径的信号仍然如常.这种不平衡使胰岛素抵抗者有更多的患高血压及动脉粥样硬化的倾向.肾素血管紧张素系统(RAS)在心血管系统的全身及局部都有表达.胰岛素抵抗上调局部RAS反应,这对高血压、心衰及动脉粥样硬化都有作用.血管紧张素Ⅱ损伤胰岛素信号转导途径,通过NF-κB途径产生炎症,减少一氧化氮的利用及促进血管收缩,从而导致胰岛素抵抗和血管内皮功能障碍.因此,RAS,胰岛素抵抗和炎症的共存协同导致内皮功能紊乱、血管损伤及动脉粥样硬化.RAS的抑制使心血管和肾脏疾病的发病率及死亡率及新发的2型糖尿病的发病率下降.