DeBoer Mark Daniel
Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA.
Nutrition. 2008 Sep;24(9):806-14. doi: 10.1016/j.nut.2008.06.013.
Cachexia is a constellation of symptoms that amount to body wasting in the setting of a variety of chronic illnesses, including cancer, heart failure, chronic kidney disease, and acquired immunodeficiency syndrome. Cachexia is particularly worrisome clinically because it is associated with a worsened prognosis of the underlying disease. Despite a large amount of study in this area, no single agent has been shown to have consistent efficacy in human trials. One promising class in this setting is ghrelin receptor agonists. Ghrelin binds to the growth hormone secretagogue-1a receptor in appetite-regulating centers in the brain, increasing expression of neuropeptide Y and agouti-related peptide during short-term treatment. Ghrelin has also been shown to have anti-inflammatory properties, which is significant, given that cachexia is thought to be produced at least partly by inflammation induced by the underlying disease. Animal studies have demonstrated efficacy using growth hormone secretagogue receptor agonists to treat cachexia caused by cancer, chemotherapy, and chronic kidney disease. Limited human trials using ghrelin or ghrelin receptor agonists in cancer and heart disease have shown improved appetite and body mass during treatment, although longer-term trials are needed to confirm sustained effects. Also uncertain--but an intriguing possibility--is whether the improved weight gain with ghrelin treatment might also lessen the severity of the underlying disease and improve outcomes.
恶病质是一组症状，在包括癌症、心力衰竭、慢性肾病和获得性免疫缺陷综合征等多种慢性疾病的情况下会导致身体消瘦。恶病质在临床上尤其令人担忧，因为它与基础疾病预后恶化相关。尽管在该领域进行了大量研究，但在人体试验中尚未显示单一药物具有一致的疗效。在这种情况下，一类有前景的药物是胃饥饿素受体激动剂。胃饥饿素与大脑食欲调节中心的生长激素促分泌素-1a受体结合，在短期治疗期间增加神经肽Y和刺鼠相关肽的表达。胃饥饿素还被证明具有抗炎特性，鉴于恶病质被认为至少部分是由基础疾病诱导的炎症产生的，这一点很重要。动物研究已证明使用生长激素促分泌素受体激动剂治疗由癌症、化疗和慢性肾病引起的恶病质有效。在癌症和心脏病中使用胃饥饿素或胃饥饿素受体激动剂的有限人体试验表明，治疗期间食欲和体重有所改善，尽管需要长期试验来确认持续效果。同样不确定但令人感兴趣的可能性是，胃饥饿素治疗带来的体重增加改善是否也可能减轻基础疾病的严重程度并改善预后。
