Glycerol may reduce intestinal mucosal barrier damage in sepsis mice through aquaporin 3

Abstract

Abstract: Objective To explore the protective effect of oral glycerol on sepsis induced intestinal mucosal barrier function. Methods Mice were randomly divided to four groups: sham operation (n=6); sham operation with oral glycerol (n=6); Mouse sepsis model (n=30)was established using cecal ligation and puncture (CLP), of which 24 mice were executed at 0, 6, 12 and 24 h after CLP respectively (6 mice at each time point) as a time-dependent group,and sepsis with oral glycerol group (n=6). Besides the time-dependent group, four groups of mice were executed at 24 h after modeling. Blood and intestinal mucosal tissue samples were collected. HE staining was used to detect pathological damage of intestinal mucosa. The plasma diamine oxidase (DAO) concentration and intestinal- type fatty acid-binding protein 2(FABP2) concentration were measured by ELISA to assess intestinal mucosal permeability. Immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of AQP3 in intestinal mucosa. Results Sepsis induced morphological damage of intestinal mucosa, and the ChiÚs score increased in a time-dependent manner (P＜0.05). The concentrations of DAO and FABP2 in plasma were significantly increased (P＜0.05), and the expression of AQP3 significantly down-regulated with the aggravation of injury (P＜0.05). The administration of oral glycerol partially improved the sepsis-induced injury of the intestinal mucosa, as shown by partial recovery of the morphological structure, with decreased ChiÚs score, decreased plasma concentrations of DAO and FABP2 (sepsis vs sepsis+glycerol, P＜0.05). Conclusions Oral treatment with glycerol may alleviate intestinal mucosal barrier damage in sepsis mice through aquaporin-3. The specific mechanism needs to be further studied.

Key words: sepsis, intestinal injury, aquaporin 3, glycerol

CLC Number:

R363

HE Rui, ZHU Ye-ke, TENG Wen-bin, SHAN Yue, YI Sheng-hua, ZHU Sheng-mei, LI Yu-hong. Glycerol may reduce intestinal mucosal barrier damage in sepsis mice through aquaporin 3[J]. Basic & Clinical Medicine, 2020, 40(5): 655-661.

References

[1]Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3)[J]. JAMA, 2016, 315: 801-810.
[2]Hassan U, Ghonge T, Reddy B, Jr. et al. A point-of-care microfluidic biochip for quantification of CD64 expression from whole blood for sepsis stratification[J]. Nat Commun, 2017,8:15937-15949
[3]Meng M, Klingensmith NJ, Coopersmith CM. New insights into the gut as the driver of critical illness and organ failure[J]. Curr Opin Crit Care, 2017, 23: 143-148.
[4]Zhu C, Chen Z, Jiang Z. Expression, distribution and role of aquaporin water channels in human and animal stomach and intestines[J]. Int J Mol Sci, 2016, 17:1381-1399
[5]Buras JA, Holzmann B, Sitkovsky M. Animal models of sepsis: setting the stage[J]. Nat Rev Drug Discov, 2005, 4: 854-865.
[6]Thiagarajah JR, Zhao D, Verkman AS. Impaired entero-cyte proliferation in aquaporin-3 deficiency in mouse models of colitis[J]. Gut, 2007, 56: 1529-1535.
[7]Chiu CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal[J]. Arch Surg, 1970, 101: 478-483.
[8]Li Y, Ren J, Wu X, et al. Intra-abdominal infection combined with intra-abdominal hypertension aggravates the intestinal mucosal barrier dysfunction[J]. Biosci Rep, 2018, 38. doi:10.1042/BSR20170931.
[9]Treskes N, Persoon AM, van Zanten ARH. Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric ischemia: a systematic review and meta-analysis[J]. Intern Emerg Med, 2017,2:821-836.
[10]Zhi X, Tao J, Li Z, Jiang B, et al. miR-874 promotes intestinal barrier dysfunction through targeting AQP3 following intestinal ischemic injury[J]. FEBS Lett, 2014, 588: 757-763.
[11]Su Z, Zhi X, Zhang Q, et al. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier[J]. FEBS Lett, 2016, 590: 1354-1364.
[12]Ikarashi N, Kon R, Sugiyama K. Aquaporins in the colon as a new therapeutic target in diarrhea and constipation[J]. Int J Mol Sci, 2016, 17: 1162-1172.
[13]Zhang D, Zhang K, Su W, et al. Aquaporin-3 is down-regulated in jejunum villi epithelial cells during enterotoxigenic Escherichia coli-induced diarrhea in mice[J]. Microb Pathog, 2017, 107: 430-435.
[14]Kon R, Tsubota Y, Minami M, et al. CPT-11-induced delayed diarrhea develops via reduced aquaporin-3 expression in the colon[J]. Int J Mol Sci, 2018, 19: 170-185.