Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents.
Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents.
复制标题
作者：
A. Negri
在不同的肾脏疾病中，肾纤维化可以由几种损伤机制诱导，但最终在肾脏中产生相同的纤维化变化。最近，已经研究了许多可以抑制细胞外基质（ECM）积聚的药物，这表明其在治疗纤维化肾病中具有治疗效用。吡非尼酮（PFD）是一种小分子，已在各种疾病进展性肾损伤模型中显示出疗效。PFD中明显没有毒性表明它不影响正常的ECM周转。松弛素是一种属于胰岛素样生长因子（IGF）家族的激素，具有抗纤维化特性，长期以来一直用于诱导硬皮病患者的短暂缓解。直到最近，它才在动物模型中被证明能显著减少皮质结节瘢痕。骨形态发生蛋白7（BMP-7）是转化生长因子β（TGF-β）超家族的一员，已被证明比依那普利更有效地减少肾小球和间质面积，并预防肾小球硬化。最后，肝细胞生长因子（HGF），其对各种细胞的多种生物活性，在包括肾脏在内的各种器官的再生和保护中具有器官营养作用。在各种动物模型中，内源性和外源性HGF均显示出对肾纤维化和慢性肾损伤的抑制作用。用这些新的抗纤维化药物抑制病理性ECM积累和调节纤维化机制是一个可实现的目标，并且可以提供超过目前用于治疗慢性肾脏疾病的疗法的进一步益处。
Renal fibrogenesis can be induced by several injury mechanisms in different renal diseases, but ultimately produces identical fibrotic changes in the kidney. Recently, a number of agents that can inhibit extracellular matrix (ECM) accumulation have been studied, suggesting a therapeutic utility in the treatment of fibrotic renal disease. Pirfenidone (PFD) is a small molecule that has shown efficacy in various models of renal damage with progressive disease. The apparent absence of toxicity in PFD suggests that it does not affect the normal ECM turnover. Relaxin, a hormone belonging to the insulin-like growth factor (IGF) family, has antifibrotic properties and has been used for a long time to induce transient remissions in patients with scleroderma. Only recently it has been shown to drastically reduce corticomedular scarring in animal models. Bone morphogenetic protein 7 (BMP-7), a member of the transforming growth factor beta (TGF-beta) superfamily, has been shown to reduce glomerular and interstitial area, and prevent glomerular sclerosis even more effectively than enalapril. Finally, hepatocyte growth factor (HGF), with its multiple biological activities on a wide variety of cells, has an organotrophic role in the regeneration and protection of various organs including the kidney. Both endogenous and exogenous HGF have shown suppressive effects on renal fibrosis and chronic renal damage in various animal models. The inhibition of pathological ECM accumulation and the modulation of fibrotic mechanisms with these new antifibrotic agents is an achievable goal and could confer further benefits beyond the current therapies used in the treatment of chronic renal diseases.