Role of using two-route ulinastatin injection to alleviate intestinal injury in septic rats.
10.1016/j.cjtee.2018.05.002
- Author:
Xue-Lian LIAO
1
;
Qu-Zhen DANZENG
2
;
Wei ZHANG
3
;
Chen-Shu HOU
1
;
Bin-Bin XU
1
;
Jie YANG
1
;
Yan KANG
4
Author Information
1. Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
2. Department of Critical Care Medicine, Tibet Autonomous Region People's Hospital, Lhasa 850000, Tibet, China.
3. Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, Guizhou Province, China.
4. Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: kang_yan_123@163.com.
- Publication Type:Journal Article
- Keywords:
Elastase;
Intestines;
Sepsis;
Trypsin;
Ulinastatin
- MeSH:
Animals;
Cadherins;
metabolism;
Cytokines;
metabolism;
Disease Models, Animal;
Glycoproteins;
administration & dosage;
pharmacology;
Inflammation Mediators;
metabolism;
Injections, Intralesional;
Injections, Intravenous;
Intestinal Diseases;
drug therapy;
etiology;
metabolism;
Intestinal Mucosa;
metabolism;
pathology;
Intestines;
Leukocyte Elastase;
metabolism;
Male;
Mucin-2;
metabolism;
Rats, Wistar;
Sepsis;
complications;
Trypsin;
metabolism;
Trypsin Inhibitors;
administration & dosage;
pharmacology
- From:
Chinese Journal of Traumatology
2018;21(6):323-328
- CountryChina
- Language:English
-
Abstract:
PURPOSE:Early application of protease inhibitors through the intestinal lumen could increase survival following experimental shock by blocking the pancreatic digestive enzymes. Hence, it was hypothesized that two-route injection (intraintestinal + intravenous) of ulinastatin (UTI), a broad-spectrum protease inhibitor, could better alleviate intestinal injury than single-route injection (either intravenous or intraintestinal).
METHODS:A sepsis model induced by lipopolysaccharide on rats was established. The rats were randomly divided into five groups: sham, sepsis, UTI intravenous injection (Uiv), UTI intraintestinal injection (Uii), and UTI intraintestinal + intravenous injection (Uii + Uiv) groups. The mucosal barrier function, enzyme-blocking effect, levels of systemic inflammatory cytokines, and 5-day survival rate were compared among groups. The small intestinal villus height (VH), crypt depth (CD), and two components of mucosal barrier (E-cadherin and mucin-2) were measured to evaluate the mucosal barrier function. The levels of trypsin and neutrophil elastase (NE) in the intestine, serum, and vital organs were measured to determine the enzyme-blocking effect.
RESULTS:Compared with the single-route injection group (Uiv or Uii), the two-route injection (Uii + Uiv) group displayed: (1) significantly higher levels of VH, VH/CD, E-cadherin, and mucin-2; (2) decreased trypsin and NE levels in intestine, plasma, and vital organs; (3) reduced systemic inflammatory cytokine levels; and (4) improved survival of septic rats.
CONCLUSION:Two-route UTI injection was superior to single-route injection in terms of alleviating intestinal injury, which might be explained by extensive blockade of proteases through different ways.
