ABSTRACT
Objective To observe the effect of parecoxib on intestinal barrier function of septic mice.Methods Sepsis was induced by cecal ligation and puncture (CLP) model.Twenty-one male C57BL/6 mice were randomly divided into three groups (n =7 in each group):group Sham,group CLP,group P (parecoxib 2 mg/kg was administered via gastric tube 2 h after CLP).In vivo intestinal permeability was measured using an in vivo ligated loop model 24 h after surgery.Twenty-one male C57BL/6 mice were randomly divided into three groups as before.The small intestine tissue sample was harvested 24 h after surgery.The intestinal pathological changes were observed under light microscope.The expression of tight junction proteins ZO-1,Occludin,and Claudin-1 in the ileum were measured by Western blot.IL-6 and PGE2 level in the ileum were measured by ELISA.Results Compared with group Sham,the intestinal permeability was significantly increased and there was a significant intestinal pathological injury in group CLP.IL-6 and PGE2 level in the ileum was sig nificantly increased and the expression of tight junction protein ZO-1,Occludin,and Claudin-1 in the ileum were reduced in the group CLP (P＜0.05).Compared with the group CLP,intestinal permeability and pathological injury was significantly reduced in the group P.The levels of IL-6 and PGE2 were significantly decreased (P＜0.05),the expression of ZO-1,Occludin,and Claudin 1 were upregulated in group P (P＜0.05).Conclusion Parecoxib can decrease the levels of proinflammatory factors and up-regulate the expression of tight junction to reverse intestinal barrier dysfunction caused by sepsis in mice.
ABSTRACT
Objective To observe the influence of silent information regulator factor 1(SIRT1)on TNF-αinduced intestinal epi-thelial Caco-2 cell barrier function destroy and to investigate its molecular machenism.Methods Caco-2 cells were randomly divided into three groups:normal control group (control),TNF-αgroup (TNF-α,100 ng/mL for 24 h)and 100 ng/mL plus 40μm resvera-trol group (TNF-α+Res).Transepithelial electrical resistance (TER)was determined.SIRT1 and the protein expressions of ZO-1 , occludin were examined by using Western blot.Results The relative expression amounts of SIRT1 protein were 0.81 ± 0.02, 0.43±0.04 and 0.60±0.03 respectively.TER of three groups were (154.00±5.00),(97.00±4.00)and(128.00±6.00)Ohm/cm2 respectively.Compared with the control group,the expression of SIRT1 protein was reduced by 47% and TER was decreased by 37.00% in the TNF-αgroup.After resveratrol precondition,TER was increased by 32.00% compared with the TNF-αgroup. The relative expression amounts of ZO-1 and occludin protein in the control group,TNF-αgroup and TNF-α+Res group were (0.62±0.06,0.57±0.03),(0.23±0.05,0.33±0.04)and(0.41±0.03,0.50±0.02)respectively.After TNF-αtreatment,the ex-pressions of ZO-1 and occludin protein were significantly deceased(P<0.05),but the resveratrol precondition could attenuate this phenomenon,compared with TNF-αgroup,the protein expression was increased by 78.00% and 51.00% respectively (P<0.05). Conclusion Under the condition of TNF-αtreatment,the SIRT1 level is decreased,but increasing SIRT1 level could increase the in-testinal tight j unction protein ZO-1 and occludin protein expression,thus alleviate the damage of TNF-αon the epithelial barrier function constituted by Caco-2 cells.