Parkin介导的线粒体自噬对急性缺血再灌注损伤诱导肾间质纤维化的作用及机制

纤维化是慢性肾脏疾病的最终共同表现。纤维母细胞激活导致肾脏纤维化，但骨髓来源的纤维母细胞的作用目前仍有争议。线粒体自噬是一种特异性的自噬，在维持细胞稳态过程中具有重要意义，已有研究表明促进线粒体自噬能够改善肾损伤。作为线粒体自噬重要的调控因子，Parkin可能抑制TGF-β和IL-6表达以及炎症反应，发挥拮抗肾小管萎缩和肾间质纤维化的作用。因此，本课题建立了小鼠肾脏急性缺血再灌注损伤后纤维化动物模型，借助骨髓移植的实验手段，研究Parkin介导的线粒体自噬抑制骨髓来源纤维母细胞对急性缺血再灌注损伤诱导肾间质纤维化的作用及机制。

Fibrosis is the ultimate common manifestation of chronic renal disease. The activation of fibroblast leads to renal fibrosis, but the role of fibroblasts derived from bone marrow is still controversial.Mitophagy is a specific autophagy, which plays an important role in maintaining cell homeostasis. Previous studies have shown that promoting mitophagy can improve renal damage.As an important regulator of mitophagy, Parkin may inhibit TGF- beta and IL-6 expression and inflammation, and play a role in antagonizing renal tubular atrophy and interstitial fibrosis.Therefore, we established fibrosis animal model in mice after acute renal ischemia-reperfusion injury (IRI) to study the effect of Parkin mediated mitophagy on bone marrow derived fibroblasts against IRI induced renal interstitial fibrosis.