胆绿素还原酶A（BVRA）通过Nrf2/ARE信号通路调节肾脏纤维化的机制

Ischemia-reperfusion injury is one of the common causes of acute kidney injury,renal fibrosis is chronic kidney disease progression to end-stage joint pathology,often leading to kidney failure and death, but it still lacks effective treatment.Numerous studies show that BVRA is the cellular redox cycle important regulator.Meanwhile BVRA plays an important role on signal transduction, gene regulation,cell growth and apoptosis, in addition BVRA was important role on diabetes, cancer and Alzheimer's disease. Our previous study found that over-expressed biliverdin reductase A macrophages make IL-10 expression is increased, while the lowexpressed biliverdin reductase A macrophages can reduce the expression of IL-10, there is the potential for renal protection, and also found that both in AKI model and overexpression BVRA macrophages NRF2 expression increased Therefore, we use NRF2 knockout mice as experimental subjects, observe biliverdin reductase A on renal fibrosis by molecular biology, cellular immunology and pathology, renal fibrosis adjustment mechanism by observing NRF2 / ARE signaling pathway, to verify our findings and identify new scientific problems. Thus providing a theoretical basis and experimental foundation to elucidate the pathogenesis of renal fibrosis and prevention strategies.

缺血再灌注损伤是急性肾脏损伤的常见原因之一， 肾脏纤维化是各种慢性肾脏疾病进展至终末期的共同病理变化，往往导致肾功能衰竭而致命，但至今仍缺乏有效的治疗措施。大量研究表明BVRA是细胞氧化还原反应循环中重要的调节者。同时BVRA在信号传导、基因调控、细胞生长和凋亡中发挥重要作用，另外BVRA在糖尿病、肿瘤和阿尔茨海默病中扮演者重要角色。我们前期研究结果发现过表达胆绿素还原酶巨噬细胞可以使IL-10表达增加，而低表达过胆绿素还原酶巨噬细胞可以使IL-10表达降低，对肾脏有潜在保护作用，并发现AKI模型和过表达BVRA的巨噬细胞中NRF2的表达增加。故我们以NRF2敲除鼠为实验对象，通过分子生物学，组织病理学和细胞免疫学观察胆绿素还原酶对肾脏纤维化的影响，通过观察NRF2/ARE信号通路调节肾脏纤维化的机制，验证我们的发现，并发现新的科学问题。从而为阐明肾脏纤维化的发病机制和防治策略提供理论依据

缺血再灌注损伤是急性肾脏损伤的常见原因之一，肾脏纤维化是各种慢性肾脏疾病进展至终末期的共同病理变化，往往导致肾功能衰竭而致命，但至今仍缺乏有效的治疗措施。大量研究表明BVRA是细胞氧化还原反应循环中重要的调节者。同时BVRA在信号传导、基因调控、细胞生长和凋亡中发挥重要作用，另外BVRA在糖尿病、肿瘤和阿尔茨海默病中扮演者重要角色。我们研究结果发现过表达胆绿素还原酶巨噬细胞可以使IL-10表达增加，而低表达过胆绿素还原酶巨噬细胞可以使IL-10表达降低，对肾脏有潜在保护作用，在人体肾穿标本中发现，CD68high组与CD68low组相比,CD68high组患者病理染色显示毛细血管内膜细胞过多，肾小管萎缩/间质纤维化，动脉透明变性明显加重，CD4+细胞，CD8+细胞，CD20+细胞明显增多，临床数据中，CD68high组患者24小时尿蛋白明显增多，高血压分级更高，EGFR下降更加明显。这为以后肾脏纤维化早期防治策略提供理论依据。