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Gut Barrier Dysfunction Induced by Aggressive Fluid Resuscitation in Severe Acute Pancreatitis is Alleviated by Necroptosis Inhibition in Rats

Cui, Qing-Rui*; Ling, Yi-Hong†,‡; Wen, Shi-Hong*; Liu, Ke-Xuan§; Xiang, Yu-Ke||; Yang, Wen-Jing; Shen, Jian-Tong*; Li, Yun-Sheng*; Yuan, Bao-Long*; Huang, Wen-Qi*

doi: 10.1097/SHK.0000000000001304
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ABSTRACT Fluid resuscitation is the first-line antishock treatment in severe acute pancreatitis (SAP). Currently, although mentions of complications related to aggressive fluid resuscitation are very frequent, a lack of proper handling of complications remains. One of the most important complications is intestinal barrier injury, including intestinal ischemia-reperfusion injury following aggressive fluid resuscitation. Once injured, the intestinal barrier may serve as the source of additional diseases, including systemic inflammatory response syndrome and multiple organ dysfunction syndrome, which aggravate SAP. This study focused on the underlying mechanisms of gut barrier dysfunction in rats induced by aggressive fluid resuscitation in SAP. This study further indicated the important role of necroptosis in intestinal barrier injury which could be relieved by using necroptosis-specific inhibitor Nec-1 before aggressive fluid resuscitation, thus reducing intestinal barrier damage. We also found pancreas damage after intestinal ischemia/reperfusion challenge and indicated the effects of high mobility group protein B1 in the vicious cycle between SAP and intestinal barrier damage.

*Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China

§Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China

||Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

Department of Anesthesiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China

Address reprint requests to Shi-Hong Wen, MD, PhD, Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2th Road, Guangzhou 510080, China. E-mail: wenshihong2006@aliyun.com; Co-correspondence: Wen-Qi Huang, MD, PhD, Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2th Road, Guangzhou 510080, China. E-mail: scorpiosslove@aliyun.com

Received 29 September, 2018

Revised 22 October, 2018

Accepted 5 December, 2018

Q-RC and Y-HL contributed equally to this study.

This work was supported by grants from National Natural Science Foundation of China (No: 81171847 to K-XL, No: 81801895 to Y-HL, and No: 81772116 to S-HW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors report no conflicts of interest.

© 2019 by the Shock Society