Protection effect of dexmedetomidine against sepsis-induced intestinal mucosal barrier injury by up-regulating hypoxia inducible factor-1ɑ in rats
10.12092/j.issn.1009-2501.2021.12.007
- Author:
Hui LI
1
;
Jun LI
1
;
Suqin HUAN
2
;
Yuhong LI
2
;
Jun FAN
3
Author Information
1. Department of Anesthesiology, Shulan (Hangzhou) Hospital
2. Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University
3. Department of Anesthesiology, Jinjiang City Hospital (Shulan Medical Jinjiang Hospital)
- Publication Type:Journal Article
- Keywords:
Dexmetomidine;
Hypoxia inducible factor-1ɑ;
Intestinal mucosal permeability;
Sepsis;
Tight junction protein
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2021;26(12):1386-1392
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To explore the protective effect and mechanism of dexmedetomidine on intestinal mucosal barrier injury in septic rats. METHODS: Forty eight SD rats were randomly divided into four groups (n=12): sham operation group (sham group), sepsis group (sepsis group), sepsis + dexmedetomidine group (DEX group), and sepsis + DEX + HIF-1ɑ inhibitor Bay87-2243 (Bay87-2243 group). Sepsis model was established by cecal ligation and perforation (CLP). The rats in both DEX and Bay87-2243 groups were given 30 μg/kg of DEX intraperitoneally 30 minutes before CLP and 2 hours after CLP; while the rats in Bay87-2243 group received oral gavage of Bay87-2243 (9 mg/kg) for 3 days before CLP. The other groups were intraperitoneally injected and orally with the same amount of normal saline. The HIF-1ɑ and the tight junction protein (tight junction protein, TJs) was detected by western blot; the plasma concentrations of diamine oxidase (DAO), intestinal fatty acid binding protein (FABP2) and D-lactic acid (D-LAC) were detected by ELISA; the morphological changes of intestinal mucosa were detected by HE staining. RESULTS: DEX significantly increased the expression level of HIF-1ɑ (P<0.05) on intestinal mucosa in rats with sepsis injury (P<0.05), thus ameliorated intestinal mucosal pathological injury, reduced Chiu's score (P<0.05), decreased intestinal mucosal permeability (P<0.05), and up-regulated TJs protein expression (P<0.05). Moreover, effect on sepsis induced intestinal mucosal injury of DEX was reversed by HIF-1ɑ Bay87-2243. CONCLUSION: DEX could protect against sepsis-induced intestinal mucosal injury by up-regulating HIF-1ɑ expression in rats.
