The Effect Of Verapamil On Gut Injury After Intestinal Ischemia Reperfusion In Rats And The Mechanism Of Action

Objective:To investigate the effect of Verapamil ,a calcium channel blockers(CCBs),on gut injury following intestinal ischemia reperfusion in rats and the mechianism of action.Methods: 21 male SD rats were randomly divided into 3 groups(n=7) :Sham-operation group(A group),Ischemia reperfusion group(I/R group)(B group)and Verapamil group(C group).Intestinal ischemia-reperfusion was initiated by clamping the superior mesenteric artery(SMA)45min followed by reperfusion. The animals in Verapamil group were given 0.5g/L verapamil 1mg/kg at 10 min before reperfusion through the caudal vein.2 hours later,terminal ileum was taken to investigate histological change and the expressions of TNF-α,Bax and Bcl-2 in the small bowel cell.Results: 1). Intestinal mucosa in the Sham-operation group was almost normal,in which histopathologic injury scores were 0.57±0.35, optical density(OD) of TNF-α,Bax and Bcl-2 were0.084±0.008,0.112±0.013 and 0.297±0.012;Intestinal mucosal lesions in the I/R group were serious with a few denuded villi, in which histopathologic injury scores were 3.29±0.57, optical density(OD) of TNF-α,Bax and Bcl-2 were0.219±0.012,0.290±0.013 and 0.106±0.008.Also,Animals in I/R group had significantly higher histological scores and expressions of TNF-α,Bax in the small bowel cell ,but lower expressions of Bcl-2 than Sham-operation group(P<0.01); 2).Intestinal mucosal lesions in the Verapamil group were middling with the develop of subepithelial space at the apex of the villus, in which histopathologic injury scores were 2.05±1.23, optical density(OD) of TNF-α,Bax and Bcl-2 were0.121±0.008,0.200±0.010 and 0.205± 0.008.Animals treated with verapamil had significantly less histological scores and expressions of TNF-α,Bax in the small bowel cell ,but higher expressions of Bcl-2 than I/R group(P<0.01).Conclusion: 1). Histological change of the small bowel is serious followed ischemia reperfusion injury.2). Verapamil has protective effect on gut injury following intestinal ischemia reperfusion in rats.3). The mechianism of action that verapamil protect gut injury may be:①inhibit the release of TNF-αwhereafter preventing the death of the small bowel cell;②prvent calcium overload,then down-regulate the expression of Bax and up-regulate the expression of Bcl-2,finally inhibit the apoptosis of small bowel cell.