Clarification of multi-functions of macrophage populations in renal fibrosis and therapeutic strategies

为阐明巨噬细胞在肾纤维化中的功能作用，并在此基础上探讨治疗难治性疾病的有效策略，本研究采用顺铂（DDP）诱导的慢性肾纤维化大鼠模型，注射抗炎药地塞米松（DX）。结果，DX注射减少了ED 1阳性渗出物巨噬细胞的数量，导致进行性肾纤维化的减少。然而，ED 2阳性驻留巨噬细胞和OX 6阳性抗原呈递巨噬细胞的出现不受DX注射的影响。此外，同时向大鼠肾间质细胞（NRK-49 F）和大鼠未分化间充质细胞（MT-9）中加入TGF-β1（一种纤维化因子）和DX减少了对α-平滑肌肌动蛋白（α-SMA）反应的细胞数量。这些体内和体外研究的结果表明，DX通过减少肾脏纤维化的发生来改善进行性肾纤维化。 关于我们 减少TGF-β1诱导的ED 1阳性巨噬细胞数量和α-SMA阳性肌纤维母细胞的形成。使用急性大鼠肾纤维化模型，研究了饮食红豆（Vigna angularis）的作用，结果，给予红豆显著减少ED 1阳性巨噬细胞的数量，并减轻肾纤维化。本实验采用硫代乙酰胺诱导的大鼠肝纤维化模型，研究了枯否细胞功能抑制剂GdCl_3对大鼠肝纤维化的影响。结果，用GdCl_3处理减少了不同巨噬细胞群体的数量，特别是改善了门静脉周围区域的纤维化。本研究阐明了巨噬细胞群在肾纤维化中的某些作用，并提供了一些可能用于人类医学的治疗方法，但仍处于实验水平。少

The purposes of this study were to clarify the functional roles of macrophages appearing in the renal fibrosis, and to explore the useful therapeutic strategies for the intractable diseases, on the basis of the data.Dexamethasone (DX), an anti-inflammatory drug, was injected in rat models of chronic renal fibrosis induced by cisplatin. As a result, the DX injection decreased the number of ED1-positive exudate macrophages, leading to the reduction of the progressive renal fibrosis. However, the appearance of ED2-positive resident macrophages and OX6-positive antigen presenting macrophages were not influenced by the DX injection. In addition, the concomitant addition of TGF-β1 (a fibrogenic factor) and DX to rat renal interstitial cells (NRK-49F) and rat undifferentiated mesenchymal cells (MT-9) decreased the number of cells reacting to α-smooth muscle actin (α-SMA). These findings of in vivo and in vitro studies indicate that DX ameliorates the progressive renal fibrosis through the dec … More reased number of ED1-positive macrophages and the reduction of the formation of α-SMA-positive myofibroblastic cells induced by TGF-β1. Using acute rat renal fibrosis model, the effect of dietary azuki bean (Vigna angularis) was investigated as a result, the administration with azuki bean dramatically decreased the number of ED1-positive macrophages, and reduced the renal fibrosis. It is shown nutritionally that the azuki bean may contain a substance which is able to reduce the renal fibrosis.Using rat hepatic fibrosis model induced by thioacetoamide, of which the pathogenesis is similar to that of renal fibrosis, the influence of GdCl_3, an inhibitor of Kupffer cell functions, was investigated. As a result, the treatment with GdCl_3 reduced the number of different macrophage populations, and in particular, fibrosis around the periportal areas was improved. These data shout be referred to the understanding of the pathogenesis of renal fibrosis.The present studies clarified some functions of macrophage populations appearing in renal fibrosis, and provided some useful therapeutic methods which may be used in human medicine, though at experimental levels. Less