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自噬调控影响重症急性胰腺炎小鼠的预后。

Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.

出版信息

Dig Dis Sci. 2018 Oct;63(10):2639-2650. doi: 10.1007/s10620-018-5053-0. Epub 2018 Apr 9.

Abstract

BACKGROUND

Acute pancreatitis (AP) is a common inflammatory disease that may develop to severe AP (SAP), resulting in life-threatening complications. Impaired autophagic flux is a characteristic of early AP, and its accumulation could activate oxidative stress and nuclear factor κB (NF-κB) pathways, which aggravate the disease process.

AIM

To explore the therapeutic effects of regulating autophagy after the onset of AP.

METHODS

In this study, intraperitoneal injections of 3-methyladenine (3-MA) and rapamycin (RAPA) in the L-arginine or cerulein plus lipopolysaccharide (LPS) Balb/C mouse model. At 24 h after the last injection, pulmonary, intestinal, renal and pancreatic tissues were analyzed.

RESULTS

We found that 3-MA ameliorated systemic organ injury in two SAP models. 3-MA treatment impaired autophagic flux and alleviated inflammatory activation by modulating the NF-κB signaling pathway and the caspase-1-IL-1β pathway, thus decreasing the injuries to the organs and the levels of inflammatory cytokines.

CONCLUSION

Our study found that the regulation of autophagy could alter the progression of AP induced by L-arginine or cerulein plus LPS in mice.

摘要

背景

急性胰腺炎(AP)是一种常见的炎症性疾病,可能发展为重症急性胰腺炎(SAP),导致危及生命的并发症。自噬通量的受损是早期 AP 的特征,其积累可能会激活氧化应激和核因子 κB(NF-κB)途径,从而加重疾病进程。

目的

探讨 AP 发病后调节自噬的治疗效果。

方法

在本研究中,采用腹腔内注射 3-甲基腺嘌呤(3-MA)和雷帕霉素(RAPA)在 L-精氨酸或亮抑蛋白酶原加脂多糖(LPS)Balb/C 小鼠模型中。在最后一次注射后 24 小时,分析肺、肠、肾和胰腺组织。

结果

我们发现 3-MA 改善了两种 SAP 模型中的全身器官损伤。3-MA 治疗通过调节 NF-κB 信号通路和半胱天冬酶-1-IL-1β通路来损害自噬通量并减轻炎症激活,从而减少器官损伤和炎症细胞因子水平。

结论

我们的研究发现,自噬的调节可以改变由 L-精氨酸或亮抑蛋白酶原加 LPS 诱导的小鼠 AP 的进展。

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