HIF-1α、iNOS在溃疡性结肠炎中的表达及临床意义

Expression of hypoxia-inducible factor-1 alpha (HIF-1α) and inducible nitric oxide synthase (iNOS) in ulcerative colitis (UC)

目的探讨低氧诱导因子-1α(HIF-1α)、诱导型一氧化氮合酶(iNOS)在溃疡性结肠炎(UC)组织中的表达及与疾病活动性的关系。方法采用免疫组织化学方法检测51例UC患者(活动期38例、缓解期13例)和20例正常对照组中的HIF-1α、iNOS表达。结果UC患者活动期HIF-1α表达显著高于正常人,差异有显著性(153.29±15.26vs193.28±16.65,P<0.01),缓解期HIF-1α表达与正常人差异无显著性(185.45±12.08vs193.28±16.65,P>0.05),HIF-1α的表达与Walmsley评分标准呈正相关;iNOS在溃疡性结肠炎患者活动期的表达显著高于正常人,差异有显著性(151.32±14.62vs196.67±17.43,P<0.01),缓解期的表达与正常人差异无显著性(189.93±15.20vs196.67±17.43,P>0.05),iNOS的表达与Walmsley评分标准也呈正相关;HIF-1α和iNOS在溃疡性结肠炎中表达水平呈正相关(r=0.627,P<0.05)。结论HIF-1α和iNOS均参与了溃疡性结肠炎的发病且与疾病的活动性有关,HIF-1α作为一种转录因子可能是iNOS基因表达中的一个重要调节者。

Objective To investigate the expression of HIF-1α and iNOS in the tissues of UC and their relationships with activity of UC. Methods Immunohistochemistry assay was performed to detect the expression of HIF-1α and iNOS in 38 UC specimens in active stage, 13 at stable stage, and 20 normal control. Results The expression of HIF-1α was higher in patients with UC at active stage than that in the controls （ 153.29 ± 15.26 vs 193.28 ± 16.65, P 〈 0.01 ） , while the expression of HIF-1α in UC at stable stage was not significantly different from that in the controls （185.45 ± 12.08 vs 193.28 ± 16.65, P 〉 0.05）. The level of HIF-1α in tissues in active UC was positively correlated with the Walmsley renal scoring （r=0.531, P=0.001）. The expression of iNOS was higher in patients with UC at active stage than that in the controls （151.32 ± 14.62 vs 196.67 ± 17.43, P 〈0.01 ） , while the expression of iNOS in UC at stable stage was not significantly different from that in the controls （ 189.93 ± 15.20 vs 196.67±17.43, P〉0.05）. The level of iNOS in the tissues in active UC was positively correlated with the Walmsley renal scoring （r=0. 596, P〈0.05）. Linear correlation analysis showed that iNOS protein was positively correlated with HIF-1α （r=0.627, P〈0.05）. Conclusion HIF-1α and iNOS are involved in the pathogenesis of UC. HIF-1α as a transcriptional factors may be an essential regulator of iNOS gene expression.