Expression and its significance of receptor-interacting protein kinase 3 in ulcerative colitis / 中华消化杂志

ABSTRACT

Objective To explore the role of receptor‐interacting protein kinase 3 (RIP3)‐mediated necroptosis in ulcerative colitis (UC ) . Methods The colonic mucosa tissues of eighty‐five patients diagnosed with UC were collected .Disease staging and pathological classification of UC patients were evaluated according to Mayo standard and Truelove standard ,respectively .The expressions of RIP3 and tumor necrosis factor (TNF)‐α were detected by immunohistochemistry .The cell inflammation model in HT‐29 cells was induced by interferon (IFN)‐γ.The expression of RIP3 mRNA and interleukin (IL)‐1βmRNA was determined by real time polymerase chain reaction (RT‐PCR) .Twenty healthy individuals were studied as controls .A single factor analysis of variance was performed in the comparison among groups ,and Pearson correlation analysis was used for correlation analysis .Results Among 85 patients with UC , 27 cases were mild ,30 cases were moderate and 28 cases were severe;for pathological classification ,26 were gradeⅠ ,31 were gradeⅡ and 28 were grade Ⅲ .The Mayo score was positively correlated with pathological grade (r=0 .997 , P<0 .05) .The expression of RIP3 and TNF‐α in colonic mucosa tissues of UC group increased along with the pathological classification grade .The expression of RIP3 of gradeⅠto Ⅲ was 1 .81 ± 0 .98 ,2 .77 ± 1 .26 and 4 .86 ± 2 .77 ,respectively ,and the differences were statistically significant (F=26 .10 ,P<0 .05) .The expression of TNF‐αof gradeⅠto Ⅲ was 1 .35 ± 0 .69 ,2 .61 ± 1 .41 and 4 .43 ± 2 .17 ,respectively ,and the differences were statistically significant (F=31 .80 ,P<0 .05) .The expression of IL‐1β mRNA of IFN‐γ group ,IFN‐γ+ z‐VAD group and IFN‐γ+z‐VAD+ TNF‐αgroup was 0 .68 ± 0 .27 ,1 .47 ± 0 .12 and 1 .86 ± 0 .16 ,respectively ,and the differences were statistically significant (F=38 .45 , P<0 .05) .The expression of RIP3 mRNA of IFN‐γgroup ,IFN‐γ+z‐VAD group and IFN‐γ+z‐VAD+TNF‐αgroup was 0 .46 ± 0 .13 ,1 .21 ± 0 .29 and 2 .06 ± 0 .20 ,respectively , and the differences were statistically significant (F= 55 .15 , P< 0 .05) .Conclusions TNF‐α/RIP3 signal pathway is up‐regulated in UC .RIP3‐mediated necroptosis promotes the death of colonic epithelial cells and exacerbates inflammatory response .RIP3‐mediated necroptosis may be an important mechanism in UC .