关键词: 七叶皂苷钠, 小肠, 缺血再灌注, p38MAPK, 细胞凋亡, 细胞因子

Abstract:

Abstract:Objective  To observe the effect of sodium aescinate(SA) on p38MAPK pathway in rats with intestinal ischemia reperfusion(I/R) injury, and to charify the protective mechanism of SA. Methods Twenty-four SD rats were randomly divided into three groups with eight rats in each:control group,intestinal I/R group,SA group.In control group,superior mesenteric artery (SAM)  was separated but not clamped;in I/R and SA groups,SMA was separated and clamped for 60 min.Each rat was given different treatment before ischemia,before reperfusion and 30 min after reperfusion respectively.In control and I/R groups,saline(5 mL/kg) was injected through tail;in SA group,SA(0.9 mg/kg) was injected through tail. The levels of TNF-α,IL-6 in plasma and the activities of myeloperoxidase(MPO) and diamine oxidase(DAO),malondialdehyde(MDA) levels in plasma and intestinal tissue were measured 60 min after reperfusion,as well as the expression levels of p38MAPK and Bax proteins in intestinal tissue were examined using immunohistochemical method.Results Compared with control group,the activities of MPO,DAO and the levels of TNF-α,IL-6,MDA in plasma were significantly increased;and the activity of MPO and the  MDA levels in intestinal tissue were also significantly increased,and while the DAO activity in intestinal tissue was significantly decreased in I/R group(all P<0.01).Compared with I/R group,the activities of MPO and DAO and the levels of MDA,TNF-α,IL-6 in plasma were significantly decreased;the MPO  activity and MDA level in intestinal tissue were also significantly decreased,and while the DAO activity in intestinal tissue was significantly increased in SA group(P<0.01).The immunohistochemistry results indicated that compared with control group,the protein expression levels of p38MAPK and Bax were significantly increased in I/R and SA groups(P<0.01);compared with I/R group,the p38MAPK and Bax protein expression levels were significantly decreased in SA group(P<0.01).The correlation analysis indicated that the MPO activity,the MDA level  and the expression levels of Bax protein in intestinal tissue  and the TNF-α,IL-6 levels  in plasma were positively correlated with the expression level of p38MAPK protein (r=0.797,0.702,0.712,0.695 and 0.715，all P<0.01).Conclusion SA can protect the intestinal I/R injury,which may be mediated by reducing the release of oxygen free radicals and cytokine,inhibiting activation of neutrophils,down-regulating p38MAPK gene protein expression to inhibit intestinal tissue apoptosis.

Key words:  , sodium aescinate, intestine, ischemia/reperfusion, p38MAPK, apoptosis, cytokine