鸢尾素减轻左旋精氨酸诱导的急性胰腺炎小鼠的肠道损伤、氧化应激和内质网应激。

Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis.

机构信息

National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

出版信息

World J Gastroenterol. 2019 Dec 7;25(45):6653-6667. doi: 10.3748/wjg.v25.i45.6653.

Abstract

BACKGROUND

Acute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated.

AIM

To investigate the effect of irisin administration on intestinal injury in experimental AP.

METHODS

AP was induced in male adult mice by two hourly intraperitoneal injections of L-arginine. At 2 h after the last injection of L-arginine, irisin (50 or 250 μg/kg body weight) or 1 mL normal saline (vehicle) was administered through intraperitoneal injection. The animals were sacrificed at 72 h after the induction of AP. Intestinal injury, apoptosis, oxidative and endoplasmic reticulum (ER) stress were evaluated.

RESULTS

Administration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas, liver and lung of AP mice.

CONCLUSION

Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP.

摘要

背景

急性胰腺炎(AP)常伴有肠损伤,进而加重 AP 的进展。我们最近的研究表明,血清鸢尾素水平低与 AP 患者的不良预后相关,而鸢尾素的给予可以预防实验性 AP。然而,鸢尾素在 AP 中的肠损伤中的作用尚未得到评估。

目的

探讨鸢尾素给药对实验性 AP 中肠损伤的影响。

方法

通过腹腔内每两小时注射 L-精氨酸诱导雄性成年小鼠发生 AP。在最后一次注射 L-精氨酸后 2 小时,通过腹腔内注射给予鸢尾素(50 或 250μg/kg 体重)或 1mL 生理盐水(载体)。在 AP 诱导后 72 小时处死动物。评估肠损伤、细胞凋亡、氧化和内质网(ER)应激。

结果

鸢尾素给药显著减轻了 AP 小鼠的肠道损伤,减少了细胞凋亡,并减轻了氧化和 ER 应激。此外,鸢尾素治疗还能有效下调血清肿瘤坏死因子-α和白细胞介素-6 水平,并减轻 AP 小鼠胰腺、肝脏和肺部的损伤。

结论

鸢尾素介导的多种生理事件减轻了 AP 后的肠损伤。鸢尾素具有作为 AP 患者有效治疗方法的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04f0/6906211/d1f336cd3407/WJG-25-6653-g001.jpg

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