LncRNA通过Lgmn影响的自噬在急性心肌梗死后造影剂所致急性肾损伤中的发生机制研究

Contrast induced acute kidney injury (CI-AKI) is one important complication of ST-segment elevation-myocardial infarction (STEMI) patients after primary percutaneous coronary intervention, and it increased the risk of short- and long-term cardiac and renal adverse events. Autophagy plays an important role in AKI development. Our previous studies demonstrated that the expression of autophagy related protein-Beclin-1 is high in CI-AKI rats; lncRNA XLOC_036125 and Lgmn which be located the adjacent its space position were significant lower in CI-AKI group. Furthermore, the Lgmn gene was similar to beclin-1 in the GO analysis. However, it remains unclear whether LncRNA influences the CI-AKI development through mediating autophagy by Lgmn in renal tubular epithelial cells. Based on our previous results, we aimed to investigate: (1) Verifying the regulating effect of lncRNA XLOC_036125 targeting Lgmn and the effect of lncRNA targeting lgmn on autophagy in the CI-AKI renal tubular cell；(2)Investigating the molecular network mechanism of LncRNA-beclin-1 axis in the close to STEMI animal models and renal tubular cells.(3) verifying LncRNA - Lgmn- beclin-1 autophagy axis in STEMI patients.

急性ST段抬高心梗（STEMI）患者行直接冠脉介入治疗后造影剂所致急性肾损伤（CI-AKI）发生率高，且增加近期和远期不良心肾事件。肾小管上皮细胞的自噬在AKI的发生起着重要作用；同时，我们前期研究发现CI-AKI组的自噬相关蛋白beclin-1表达升高，LncRNA XLOC_036125和与之空间位置相邻的Lgmn表达下降，而Lgmn与beclin-1功能相似（GO分析）。然而，尚不明确LncRNA是否通过Lgmn调控自噬而影响CI-AKI发生。本课题组拟在前期研究基础上探讨（1）肾小管上皮细胞中LncRNA对Lgmn调控作用（2）LncRNA靶向Beclin-1对肾小管细胞及模拟STEMI大鼠CI-AKI自噬的调控网络（3）STEMI患者血标本验证XLOC_036125–Lgmn- Beclin-1自噬轴。

急性心肌梗死（AMI）后造影剂致急性肾损伤（CI-AKI）发生率高达26%，死亡风险增加2-9倍。既往研究表明AMI后CI-AKI发病机制不明且生物标志物存在滞后等局限性。研究内容基本按照计划安排执行。（1）本课题组创新性的采用碘普罗胺诱导大鼠造影剂所致急性肾损伤的发生，并对其肾组织行  RNA  测序。本课题基于低渗造影剂构建了造影剂所致急性肾损伤中的新型动物模型；（2）随后利用全转录测序及生信分析筛选了潜在的影响 CI‐AKI 的关键非编码分子并完成了动物及临床样本上的验证，最终验证得 lnc‐HILPDA、lnc‐PRND 为潜在的预测效能较好的两个 lncRNA；（3）经生信预测及实验验证后发现 lnc‐HILPDA—miR‐188—SRSF7 可能是 CI‐AKI 中关键的调控轴，所以对该调控轴展开初步探索。相关结果发表 SCI论文 6 篇。获得国家国家实用新型专利授权 1 项。培养硕士毕业生 2 名。4 篇相关研究成果被国内外学术会议收录或论文发言。为AMI后CI-AKI临床防治提供新型生物标志物与潜在靶点。