Chen Yan, Xiang Wei, Li Xiang, Wang Daming, Qian Chunyan
Department of Emergency, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
Drug Clinical Trial Institution, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1246-1252. doi: 10.3892/etm.2019.7711. Epub 2019 Jun 26.
The aim of the present study was to investigate the regulatory effect of rosiglitazone on the progression of acute pancreatitis (AP) and pancreas injury, and the underlying mechanism. An AP rat model was established using caerulein and validated by detection of amylase, lipase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) serum levels. Pancreatic injury was assessed by pathological examination. The expression levels of microRNA (miR)-26a in AP rats and AR42J cells were analyzed using reverse transcription-quantitative PCR (RT-qPCR). Luciferase reporter gene assay was applied for detecting whether miR-26a bound to the target gene phosphatase and tensin homolog (PTEN). The regulatory effect of rosiglitazone on the PI3K/AKT signaling pathway was analyzed by western blot analysis. Results demonstrated that establishment of an AP model was successful with severe pancreas injury and classic AP phenotypes observed in rats. Increased serum expression of amylase, lipase, TNF-α, IL-6 and TGF-β were observed in AP rats. Rosiglitazone pretreatment prevented AP progression through suppression of miR-26a expression via binding to and degrading PTEN. Western blot analysis demonstrated that rosiglitazone blocked the PI3K/AKT signaling pathway through PTEN. In conclusion, it was determined that rosiglitazone prevented AP by downregulating miR-26a via the PI3K/AKT signaling pathway.
本研究的目的是探讨罗格列酮对急性胰腺炎（AP）进展及胰腺损伤的调节作用及其潜在机制。采用雨蛙素建立AP大鼠模型，并通过检测淀粉酶、脂肪酶、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和转化生长因子-β（TGF-β）血清水平进行验证。通过病理检查评估胰腺损伤。采用逆转录-定量PCR（RT-qPCR）分析AP大鼠和AR42J细胞中微小RNA（miR）-26a的表达水平。应用荧光素酶报告基因检测法检测miR-26a是否与靶基因磷酸酶和张力蛋白同源物（PTEN）结合。通过蛋白质印迹分析罗格列酮对PI3K/AKT信号通路的调节作用。结果表明，AP模型建立成功，大鼠出现严重胰腺损伤和典型的AP表型。AP大鼠血清淀粉酶、脂肪酶、TNF-α、IL-6和TGF-β表达增加。罗格列酮预处理通过与PTEN结合并降解PTEN抑制miR-26a表达，从而阻止AP进展。蛋白质印迹分析表明，罗格列酮通过PTEN阻断PI3K/AKT信号通路。总之，研究确定罗格列酮通过PI3K/AKT信号通路下调miR-26a来预防AP。
