鱼油通过 AMPK/SIRT-1/自噬通路缓解肠缺血/再灌注引起的肝损伤。

Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion AMPK/SIRT-1/autophagy pathway.

机构信息

Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China.

Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China.

出版信息

World J Gastroenterol. 2018 Feb 21;24(7):833-843. doi: 10.3748/wjg.v24.i7.833.

AIM

To evaluate whether fish oil (FO) can protect liver injury induced by intestinal ischemia/reperfusion (I/R) the AMPK/SIRT-1/autophagy pathway.

METHODS

Ischemia in Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analyses. AMPK, SIRT-1, and Beclin-1 expression was determined in lipopolysaccharide (LPS)-stimulated HepG2 cells with or without FO emulsion treatment.

RESULTS

Intestinal I/R induced significant liver morphological changes and increased serum alanine aminotransferase and aspartate aminotransferase levels. Expression of p-AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis factor-α (TNF-α) and malonaldehyde (MDA) were increased. FO emulsion blocked the changes of the above indicators effectively. Besides, in LPS-stimulated HepG2 cells, small interfering RNA (siRNA) targeting AMPK impaired the FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-α and MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease of TNF-α and MDA.

CONCLUSION

Our study indicates that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway.

目的

评估鱼油（FO）是否可以通过 AMPK/SIRT-1/自噬途径来保护肠缺血/再灌注（I/R）引起的肝损伤。

方法

通过肠系膜上动脉闭塞 60 分钟和再灌注 240 分钟来诱导 Wistar 大鼠的缺血。每天通过腹腔注射向每个动物给予 1 毫升 FO 乳剂或生理盐水，连续 5 天。在再灌注结束时处死动物。采集血液和组织样本进行分析。在 LPS 刺激的 HepG2 细胞中，用或不用 FO 乳剂处理，测定 AMPK、SIRT-1 和 Beclin-1 的表达。

结果

肠 I/R 导致明显的肝形态学改变，并增加血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。p-AMPK/AMPK、SIRT-1 和自噬标志物的表达降低，而肿瘤坏死因子-α（TNF-α）和丙二醛（MDA）增加。FO 乳剂有效地阻止了上述指标的变化。此外，在 LPS 刺激的 HepG2 细胞中，靶向 AMPK 的小干扰 RNA（siRNA）削弱了 FO 诱导的 p-AMPK、SIRT-1 和 Beclin-1 的增加以及 TNF-α和 MDA 的减少。SIRT-1 siRNA 削弱了 SIRT-1 和 Beclin-1 的增加以及 TNF-α和 MDA 的减少。