Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Department of Critical Care Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Life Sci. 2020 Jan 15;241:117118. doi: 10.1016/j.lfs.2019.117118. Epub 2019 Nov 29.
Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP.
Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments.
MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects.
MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.
急性胰腺炎（AP）通常伴有多器官功能不全，包括肾功能损伤。高脂血症被认为是诱发 AP 的危险因素。高脂肪饮食诱导的高脂血症性胰腺炎（HP）发病率日益增高，其症状和并发症较其他 AP 更为严重。然而，关于 HP 合并急性肾损伤的详细机制或介质研究较少。本研究旨在探讨 miR-214 在 HP 中的表达情况，以及 miR-214 是否具有调节 HP 引起的病理性肾脏损伤的功能。
采用 Sprague-Dawley 大鼠建立长期高脂肪饮食和牛磺胆酸钠注射诱导的 HP 合并急性肾损伤模型。通过注射 LV-rno-miR-214-3p 或 LV-anti-rno-miR-214-3p 来外源性调节 miR-214-3p，通过一系列分子和组织学实验研究其对 HP 的影响。
miR-214-3p 在 HP 大鼠的肾脏、胰腺和血清中均上调，并可加重 HP 引起的病理改变、肾脏和胰腺损伤及纤维化。当 miR-214-3p 过表达时，HP 中的炎症反应增强。此外，miR-214-3p 上调可抑制 HP 肾脏中 PTEN 的表达，同时增加 P-Akt 水平，这可能是诱导胰腺炎严重症状的一种可能机制。miR-214-3p 下调则表现出相反的效果。
miR-214-3p 可加重 HP 合并急性肾损伤引起的组织损伤和炎症反应，为针对 miR-214-3p 治疗 HP 合并急性肾损伤提供了新的治疗视角。
