miR-21介导线粒体自噬与细胞焦亡对肾纤维化的影响及机制

肾纤维化是慢性肾脏病（CKD）发展至终末期肾病的最终共同通路。线粒体功能障碍严重影响CKD的转归，然而其机制尚不清楚。我们前期研究发现，miR-21-5p可以通过对线粒体及其代谢相关通路的调控，促进肾脏纤维化。同时，我们通过生物信息学预测发现，miR-21-5p对自噬相关多个关键分子均可能存在靶向调控。因此，我们推测miR-21-5p可能通过介导线粒体自噬，引起炎症小体活化及细胞焦亡，促进肾小管上皮细胞损伤及纤维化，从而在肾纤维化中发挥重要影响。我们将首先通过肾小管上皮细胞纤维化模型，探讨miR-21-5p介导线粒体自噬与细胞焦亡的机制；再通过肾纤维化动物模型，观察miR-21-5p对线粒体功能及肾纤维化是否具有调节作用；最后通过不同程度CKD患者肾活检标本的比较，验证miR-21-5p对线粒体及肾纤维化的影响，阐述线粒体功能障碍引起肾纤维化的有效机制，为肾纤维化的进一步研究提供理论依据。

Renal fibrosis is the ultimate common pathway for the development of chronic renal disease (CKD) to end-stage renal disease. Our previous study found that miR-21-5p can promote renal fibrosis through the regulation of mitochondria and related metabolic pathways. At the same time, through bioinformatics prediction, we found that miR-21-5p may have targeted regulation of multiple key molecules related to autophagy. Therefore, we speculate that miR-21-5p may play an important role in renal fibrosis by mediating mitochondrial autophagy, with NLRP3 inflammasome activation and pyroptosis, and promoting renal tubular epithelial cell injury and fibrosis. We will first explore the mechanism of miR-21-5p mediated mitochondrial autophagy and pyroptosis through the renal tubular epithelial cell fibrosis model. And with the animal model of renal fibrosis, it was observed whether miR-21-5p had a regulatory effect on mitochondrial function and renal fibrosis. Finally, the effects of mir-21-5p on mitochondria and renal fibrosis were verified by comparison of renal biopsy specimens from different degrees of CKD. The completion of this project will expound the effective mechanism of mitochondrial dysfunction to cause renal fibrosis and provide theoretical basis for further study of renal fibrosis.