Abstract

BackgroundMast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.Methods120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg-1, CS 50 mg·kg-1, and CP 0.75 mg·kg-1 i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.ResultsIntestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (P < 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (P < 0.05), attenuated the down-regulation or up-regulation of the above index (P < 0.05). Treatment with CP decreased the survival rate on the 3rd day after reperfusion compared with group M(P < 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(P > 0.05).ConclusionMast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.

Highlights

  • Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats

  • Cordeiro and colleagues reported that administration of diphenhydramine (50 mg/kg, H2 blocker) before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion [7]

  • The 1st to 7th day's survival rates after 90 minutes' intestine ischemia were from 33.3% to 16.7%, while the 1st to 7th day's survival rates after 120 minutes' intestine ischemia were from 16.7% to zero

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Summary

Introduction

Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats. In addition to localized tissue damages, IIRI induces inflammatory damages in remote organs, in the lung and liver, and is associated with a high mortality [3]. Previous studies demonstrated that the degranulation of IMMC can be induced by oxidants generated in the post-ischemic gut, and the released inflammatory mediators such as histamine and tumor necrosis factor-α(TNF-α) could aggravate the injury to intestine after reperfusion [5,6]. Cordeiro and colleagues reported that administration of diphenhydramine (50 mg/kg, H2 blocker) before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion [7]. The above results prove that administration of antihistaminic agents could decrease IIRI

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