肾纤维化的细胞和分子基础

The cellular and molecular basis of renal fibrosis

纤维化造成的正常肾实质破坏是导致慢性肾脏病渐进性损伤的常见致病因素。了解肾间质纤维化的发病基础可以为治疗慢性肾脏病提供更好的选择。虽然其机制较为复杂,但可主要归纳为以下四点:(1)间质性炎性反应,同时参与致病和修复过程;(2)主要来源于肾间质细胞(成纤维细胞)的肌纤维母细胞形成独特的间质细胞群,参与细胞外基质与间质瘢痕形成;(3)肾小管上皮细胞在损伤早期参与损伤过程,在损伤后期由于其再生能力的丧失成为纤维化的受害者;(4)间质毛细血管完整性的破坏导致氧输送受阻,发生恶性级联缺氧-氧化应激,加重了肾损伤和纤维化,由于缺乏足够的血管生成反应,无法维持健康的间质毛细血管网络。遗传和表观遗传因素的重要性也日益受到重视。心肾综合征的发生发展与肾脏纤维化的高发病率和病死率密切相关。

The destruction of normal kidney parenchyma caused by fibrosis is a common cause of chronic kidney disease. Understanding the pathogenesis of renal interstitial fibrosis can provide a better treatment option for chronic kidney disease. Although Complex, it can be mainly summarized as the following four aspects： （1）Interstitial inflammatory reaction, which participates in the pathogenesis and repair process. （2）Myofibroblast mainly derived from the renal in- terstitial cells （fibroblasts） forms a unique cell mass, which participates in the formation of extracellular matrix （ECM） and interstitial scars. （3）Renal tubular epithelial ceils participate in early kidney injury, and in the late kidney injury, they become the victim of fibrosis for the loss of the regenerative ability. （4）The damaged integrity of interstitial capillaries results in the disruption of oxygen transport, and the incidence of a malignant cascade of hypoxia and oxidative stress aggravates renal injury and fibrosis. Due to the lack of sufficient blood vessel formation, the healthy capillary network can not be maintained. The importance of genetic and epigenetic factors has also been paid more attention. The incidence and development of cardiac syndrome is closely related to the high morbidity and mortality of renal fibrosis.