Preventive effect of Tongxinluo on endothelial survival and vascular integrity, together with inhibition of inflammatory reaction in rats model of intestine ischemia/reperfusion injury

Pak J Pharm Sci. 2018 Nov;31(6):2403-2410.

Abstract

This study was design to investigate preventive function of Tongxinluo (TXL) capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion (I/R) injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group (10 rats each). Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-κB were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-κB. TXL pretreatment groups (TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group) significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-κB expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction.

MeSH terms

  • Angiopoietin-Like Protein 4 / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigens, CD / metabolism
  • Apoptosis / drug effects*
  • Cadherins / metabolism
  • Capillary Permeability / drug effects*
  • Cytoprotection
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Gastrointestinal Agents / pharmacology*
  • HMGB1 Protein / metabolism
  • Inflammation Mediators / metabolism*
  • Intestines / blood supply*
  • Male
  • NF-kappa B / metabolism
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • ANGPTL4 protein, rat
  • Angiopoietin-Like Protein 4
  • Anti-Inflammatory Agents
  • Antigens, CD
  • Cadherins
  • Drugs, Chinese Herbal
  • Gastrointestinal Agents
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Inflammation Mediators
  • NF-kappa B
  • cadherin 5
  • tongxinluo