Tarzi Ruth M, Cook H Terence, Jackson Ian, Pusey Charles D, Lord Graham M
Department of Renal Medicine and Transplantation, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom.
Am J Pathol. 2004 Feb;164(2):385-90. doi: 10.1016/S0002-9440(10)63128-8.
Leptin is an adipose tissue-derived hormone that signals nutritional status to the hypothalamus. Recent evidence indicates that leptin modifies proinflammatory immune responses and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin deficiency on immune-mediated renal disease, susceptibility to accelerated nephrotoxic nephritis was examined in leptin-deficient C57BL/6-ob/ob mice and C57BL/6 wild-type controls. The model was induced with sheep anti-mouse glomerular basement membrane antibody injected to mice preimmunized against sheep IgG, and mice were sacrificed 8 days after induction of disease. The leptin-deficient ob/ob mice were strongly protected from glomerular crescent formation, macrophage infiltration, glomerular thrombosis, and albuminuria in this model. Our findings suggest that leptin is required for the induction and maintenance of immune-mediated glomerulonephritis, and that blockade of the leptin axis might provide an attractive therapeutic possibility in human autoimmune disease.
瘦素是一种由脂肪组织产生的激素，可向下丘脑传递营养状态信号。最近的证据表明，瘦素可调节促炎免疫反应，并可能在营养缺乏和免疫功能障碍之间提供关键联系。为了研究瘦素缺乏对免疫介导的肾脏疾病的影响，我们检测了瘦素缺乏的C57BL/6-ob/ob小鼠和C57BL/6野生型对照对加速型肾毒性肾炎的易感性。该模型通过向预先免疫过羊IgG的小鼠注射羊抗小鼠肾小球基底膜抗体诱导而成，在疾病诱导后8天处死小鼠。在该模型中，瘦素缺乏的ob/ob小鼠受到强烈保护，免受肾小球新月体形成、巨噬细胞浸润、肾小球血栓形成和蛋白尿的影响。我们的研究结果表明，瘦素是免疫介导的肾小球肾炎诱导和维持所必需的，并且阻断瘦素轴可能为人类自身免疫性疾病提供一种有吸引力的治疗可能性。
