Ghrelin treatment of chronic kidney disease: Improvements in lean body mass and cytokine profile
Ghrelin treatment of chronic kidney disease: Improvements in lean body mass and cytokine profile
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DOI：
10.1210/en.2007-1046
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Marks, Daniel L.
中科院分区：
文献类型：
--
作者：
DeBoer, Mark D.;Zhu, Xinxia;Marks, Daniel L.
慢性肾脏疾病（CKD）与炎性细胞因子的增加有关，并可导致恶病质，伴有肌肉和脂肪储存的损失。我们先前证明了用生长素释放肽和生长素释放肽受体激动剂治疗癌症恶病质模型的功效。目前，我们研究了大鼠CKD的手术模型，导致尿毒症和瘦体重的减少。用生长激素释放肽和两种生长激素释放肽受体激动剂（BIM-28125和BIM-28131）治疗导致食物摄入增加和瘦体重增加的改善，这部分与肌肉蛋白质降解的减少有关，如通过由切割的肌动球蛋白产生的14-kDa肌动蛋白片段的肌肉水平所评估的。此外，相对于盐水处理，用生长素释放肽处理的肾切除动物中循环炎性细胞因子减少。Ghrelin治疗的动物也有脑干中IL-1受体表达的减少和激素原转化酶-2表达的减少，激素原转化酶-2是一种参与将阿黑皮素原加工成促凋亡肽α-MSH的酶。我们的结论是，生长激素释放肽治疗尿毒症改善瘦体重增加的结果，部分原因是抑制肌肉蛋白水解，并可能与肌肉的影响。
Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide alpha-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.