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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2021, Vol. 26 ›› Issue (3): 264-270.doi: 10.12092/j.issn.1009-2501.2021.03.004

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Protective effect of hypoxia inducible factor-1α on intestinal mucosal barrier in sepsis

HE Rui 1, TENG Wenbin 1, YAO Liuxu 2, SHAN Yue 2, ZHU Shengmei 1, LI Yuhong 3   

  1. 1 Department of Anesthesiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China; 2 Department of Anesthesiology, Shaoxing People's Hospital, Shaoxing 312000, Zhejiang, China; 3 Shulan Hangzhou hospital, Shulan International Medical College, Shuren University, Hangzhou 310004, Zhejiang, China
  • Received:2020-10-14 Revised:2020-12-29 Online:2021-03-26 Published:2021-04-06

Abstract: AIM: To investigate the effect and mechanism of hypoxia inducible factor-1α on intestinal mucosal barrier in sepsis.  METHODS: SD rats were randomly divided into 4 groups: sham group, sepsis group, sepsis+HIF-1α stimulant (sepsis+DMOG group), sepsis+HIF-1α inhibitor (sepsis+Bay87-2243 group), 6 rats in each group. Sepsis model was established by cecal ligation and perforation (CLP). The levels of inflammatory markers IL-1β, IL-6, TNF-α, oxidative stress markers MDA and antioxidant factors SOD and CAT were detected by ELISA and the expression of HIF-1α in intestinal mucosa was detected by Western blot. The pathological damage of intestinal mucosa was detected by HE staining. RESULTS: Inflammatory factors, oxidative stress factors and HIF-1α were significantly up-regulated in septic rats (P<0.05). The contents of IL-1β, IL-6, TNF-α and MDA in plasma were significantly decreased by intraperitoneal injection of DMOG (P<0.05); the levels of SOD and CAT in plasma were increased (P<0.05), HIF-1α was up-regulated (P<0.05), and the pathological damage of intestinal mucosa was alleviated, with decreased Chiu's score (P<0.05). Oral administration of Bay87-2243 gave the opposite result. CONCLUSION: HIF-1α has a protective effect on intestinal mucosal injury in sepsis. The mechanism may be related to the alleviation of inflammatory response and inhibition of oxidative stress.

Key words: sepsis, inflammatory response, oxidative stress response, hypoxia inducible factor-1α, hypoxia inducible factor-1α stimulant, hypoxia inducible factor-1α inhibitor

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