急性肾损伤是心脏手术围术期的严重并发症，而围术期高胆红素血症是急性肾损伤的危险因素。我们前期报道高胆红素血症会增加肾小管上皮细胞调亡并且加重肾缺血再灌注损伤（RIRI），但机制不明。近期有研究发现足细胞损伤会高表达miR-150。申请者预实验发现高胆红素血症引起足细胞足突融合、足突消失等早期损伤改变，同时会上调足细胞Cx43的表达，Cx43组成的缝隙连接可以传递miR-150模拟物。据此假设，高胆红素血症诱导足细胞早期损伤，上调Cx43，足细胞损伤产生的miR-150通过Cx43传递至足细胞及肾小管上皮细胞，抑制自噬，加重RIRI。本研究拟通过离体实验利用质粒转染和显微注射等方法验证Cx43对miR-150的通透性及活性，并在细胞和动物水平探讨Cx43传递miR-150抑制自噬在高胆红素血症加重RIRI中的机制，再通过Cx43阻滞模拟肽进行干预，为实现基于机制的治疗提供理论基础。

Acute kidney injury following cardiac surgery is a severe complication, and the hyperbilirubinemia in the perioperative period of cardiac surgery is a risk factor to acute kidney injury. Our previous data demonstrated that hyperbilirubinemia induced the apoptosis of renal tubular epithelial cell and aggravated renal ischemia reperfusion injury (RIRI). However, the mechanism remains elusive. The latest study found that injury podocytes expressed miR-150. Applicant’s preliminary experiment showed that hyperbilirubinemia leaded to early impairment of podocytes such as foot processes effaced and effacement and induced the expression of Cx43 on podocytes and that gap junction composed by Cx43 can delivery miR-150 mimics. It is hypothesized that hyperbilirubinemia up-regulates the expression of miR-150 and Cx43 in early injury podocytes and that the miR-150 is delivered to podocytes via Cx43 and to tubular epithelial cells, which inhibits autophagy, and thus aggravates RIRI. The aim of this study is to elucidate the permeability and activity of Cx43 to miR-150 by plasmid transfection and microinjection and the role of Cx43 on podocyte delivering miR-150 to inhibit autophagy in hyperbilirubinemia aggravated RIRI in vitro and in vivo, and finally the Cx43 blocker mimic peptides were investigated to achieve the mechanism-based treatment.