Action machanism of SIRT1 involves TNF-α-induced intestinal epithelial barrier destroy / 重庆医学

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 groupsnormal 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.