circ RNA-ITCH 调控miRNA-214减轻高脂血症胰腺炎大鼠肾损伤机制研究

In recent years, hyperlipidemia pancreatitis (HP) and the concurrent acute kidney injury (AKI) has attracted more and more attention, but the pathological mechanism, as well as the effective alleviative method of HP induced AKI remains to be further studied. Our previous studies indicate that Rosiglitazone could inhibit the activation of NF-κB and MAPK P38 signaling pathways, relieve inflammatory response and inhibit cell apoptosis, thus attenuating renal injury caused by HP.But the further mechanism is not clear. Domestic and international studies have shown that circ RNA-ITCH may have competitive binding miRNA-214 regulation Wnt/beta-catenin pathway to regulate the inflammatory response, cell proliferation, presumably plays an important role in the pathological process of HP and AKI, and reduce apoptosis and improve the prognosis of HP complicated AKI. This study intends to adopt the high-fat diet combined with the sodium taurocholate retrograde pancreatic duct injection method, establish a rat model of hyperlipidemia acute pancreatitis, observe the pathological features of HP induced kidney injury in rats and evaluate circ RNA-ITCH regulates the miRNA-214 expression have therapeutical effect for the complications and explore its pathological mechanism.

近年来，高脂血症性胰腺炎(HP)并发的急性肾损伤(AKI)引起越来越多的关注，但HP并发AKI的病理机制及有效的缓解手段有待于进一步研究。我们的前期研究结果显示，通过抑制NF-κB和p38MAPK信号通路，减轻炎症反应和抑制细胞凋亡可以缓解HP引发的AKI，进一步作用机制尚不明确。国内外研究显示，circ RNA-ITCH 可能通过竞争性结合miRNA-214 调控wnt/β-catenin通路达到调控炎症反应、细胞增殖的作用，推测其在HP及AKI的病理进程中均发挥重要作用；进而减少细胞凋亡并改善HP并发的AKI预后。本研究拟采用高脂饮食联合牛磺胆酸钠逆行胰胆管注射方法，建立高脂血症急性胰腺炎大鼠模型，观察HP并发的AKI的病理特点，并在此基础上初步评价circRNA-ITCH 调控miRNA-214表达对该并发症的治疗作用以及探索其病理机制。

肾功能障碍在重症急性胰腺炎中的发生率较高，进而导致的多器官功能不全是重症急性胰腺炎患者死亡的关键决定因素。高脂血症是急性胰腺炎的危险因素之一，高脂血症性胰腺炎（HP）近年来发病率呈上升趋势，与其他类型胰腺炎相比，并发症更为严重。miRNA-214-3p参与高脂血症性胰腺炎并发肾损伤的疾病发生、发展，其调控机制尚不清楚。. 本研究采用高脂饮食联合牛磺胆酸钠逆行胰胆管注射方法，建立高脂血症急性胰腺炎大鼠模型，观察HP 并发的AKI 的病理特点，监测各组大鼠肾脏、胰腺、血清中circRNA-ITCH 及miRNA-214表达情况，应用RNA干扰、拮抗干预及慢病毒转染等手段探索其调控机制。结果显示miRNA-214-3p可以通过抑制PTEN的表达引起P-Akt升高，可能调节其下游途径来加重HP模型组肾脏组织损伤和纤维化以及更严重的炎症反应。敲除miRNA-214-3p可以减轻这些损伤。在大鼠动物模型中circRNA-ITCH 未通过竞争性结合miR-214-3p 调控HP 并发的AKI。这可能为靶向治疗HP的急性肾损伤提供一定的理论与实验依据。