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β3肾上腺素受体(β3AR)是新发现的受体,主要参与脂肪组织甘油三酯的降解,产生能量;心衰时心脏中β3AR上调;心肌缺血缺氧时,内源性脂解作用可维持心肌的收缩性;为了维持心功能慢性缺血性心衰代偿期很可能存在能量代谢重建:在神经内分泌激活的同时,以外源性游离脂肪酸(FFA)为主要能量底物,心脏缺血缺氧进一步加重时,β3AR代偿性上调并介导心肌细胞的内源性脂解供能,葡萄糖经由3-磷酸甘油参与合成内源性三酰甘油再脂解而间接供能,葡萄糖的氧化被抑制,此时心肌细胞兼有类似脂肪细胞的功能。心衰时β3AR上调是能量代谢代偿的结果。但上调的β3AR长期过度激活有可能引起心肌组织继发性肉碱缺乏,导致ATP生成障碍使心衰失代偿,因而在心衰失代偿期β3AR阻滞剂可能有利于缓解心衰。而(β3AR激动药最终表现为正性肌力作用还是负性肌力作用,要看在具体的作用部位它对β3AR的直接效应与其对胰岛素的继发效应二者的力量对比)。从理论上讲,β3AR激动药用于慢性缺血性心衰代偿期,既可改善心肌的能量代谢,产生正性肌力作用,又可降低动脉血压,降低心脏的前负荷,从而改善心功能;β3AR激动药还可改善与心衰并存的胰岛素抵抗。心脏能量代谢的缺陷越来越被认为在心衰的进展中起着重要的决定性作用,心脏的代谢适应和适应不良是很有前景的药物治疗新靶点。
β3 adrenergic receptor (β3AR) is a newly discovered receptor that is mainly involved in the degradation of adipose tissue triglycerides to produce energy; β3AR upregulation in the heart during heart failure; endogenous lipolysis in myocardial ischemia and hypoxia Maintain myocardial contractility; in order to maintain cardiac function compensatory phase of chronic ischemic heart failure is likely to exist energy metabolism reconstruction: in neuroendocrine activation at the same time, exogenous free fatty acid (FFA) as the main energy substrate, cardiac ischemia When hypoxia further aggravates, β3AR compensatory up-regulates and mediates cardiomyocyte endogenous lipolytic energy supply, glucose is indirectly fed through 3-phosphoglycerate involved in the synthesis of endogenous triglyceride re-lipolysis, and glucose is oxidized Is inhibited, this time both cardiomyocytes and fat-like cells function. Heart failure, β3AR up-regulation is a result of energy metabolism. However, the prolonged overexpression of β3AR may cause secondary carnitine deficiency in myocardium, leading to dysfunction of ATP production and thus decompensation of heart failure. Therefore, β3AR blockade in decompensated heart failure may be beneficial to relieve heart failure. However, whether β3AR agonists ultimately exhibit positive or negative inotropic effects depends on the direct effect of β3AR on the specific site of action versus the secondary effect on insulin. In theory, β3AR agonist for chronic ischemic heart failure compensated, can improve myocardial energy metabolism, positive inotropic effect, but also reduce arterial blood pressure, reduce cardiac preload, thereby improving the heart Function; β3AR agonist drugs can also improve the coexistence of insulin resistance and heart failure. Defects in cardiac energy metabolism are increasingly considered to play an important decisive role in the progression of heart failure. Metabolic adaptation and maladaptation of the heart are promising new targets for drug therapy.