热休克转录因子2和促炎症细胞因子在溃疡性结肠炎中的表达研究

发布时间：2018-04-21 19:29

本文选题：热休克转录因子2 + 溃疡性结肠炎　；参考：《昆明医科大学》2014年硕士论文

【摘要】：背景：溃疡性结肠炎(Ulcerative colitis, UC)是一种肠道非特异性慢性炎性疾病,发病机制仍未明确。本病见于任何年龄,但以中青年多见,病情反复、迁延不愈,严重影响患者身心健康和社会生产力。目前UC的诊断仍主要依靠临床症状、结肠镜及病理学检查,现C反应蛋白(CRP)、血沉(ESR)、乳铁蛋白、钙卫蛋白等血清和粪便指标虽可以在一定程度上反应UC炎症活动程度,但缺乏特异性,也无法准确预测黏膜愈合。因此,筛选更具特异性和准确性的体液指标势在必行。本小组通过基因芯片、双向凝胶电泳以及质谱分析等系列研究筛选出UC患者差异表达的基因和蛋白质,发现热休克转录因子2(Heat shock factor2, HSF2)在基因及蛋白质水平表达均上调,免疫组织化学结果亦显示HSF2在UC患者肠黏膜中的表达与疾病严重程度相关。上述结果提示HSF2可能作为一项新的评估UC炎症活动程度的指标。因此,进一步研究HSF2和促炎症细胞因子表达水平与疾病活动指数的相关性,有助于探索其在UC诊治中的作用。目的：检测UC患者结肠黏膜和血清中HSF2和促炎症细胞因子(TNF-α、IL-1β、IL-8)转录和翻译水平,评价HSF2与UC病情严重程度的关系以及其与促炎症细胞因子表达的相关性。方法：收集2013年2月至2014年2月来我院住院治疗的UC患者新鲜肠黏膜组织及血清样品。选取因腹痛或腹部不适收住我院,经肠镜检查未发现有异常黏膜病变,根据罗马Ⅲ标准诊断为IBS的患者作为对照组,采集其肠黏膜组织和血清。UC病情评估采用改良Mayop评分系统(UC-DAI)。实时荧光定量PCR法检测结肠粘膜中HSF2和TNF-α、IL-1β、IL-8的mRNA转录水平。ELISA测定血清中HSF2、TNF-α、IL-1β、IL-8的含量。应用SPSS17.0统计学软件对实验数据进行统计分析,探讨HSF2和临床病情、TNF-α、IL-1β、IL-8在结肠黏膜组织及血清中表达的相关性。结果：共收集到UC活动期患者肠黏膜组织样品20例,对照组5例。UC患者血清样品60例,对照组血清样品20例。 1、UC患者结肠黏膜组织HSF2(1.300±0.107～2.204±1.190folds)、TNF-α (6.278±1.791-19.228±4.383folds)、IL-1β(48.906±13.716～212.894±29.692folds)、IL-8(27.489±4.549～124.732±26.084folds) mRNA的转录均高于对照组(P0.05)。且HSF2与TNF-α(r=0.89)、IL-β (r=0.89)、IL-8(r=0.80)的表达均具有正相关性(P0.0001)。 2、UC患者血清中HSF2(0.914±0.332～2.148±0.421ng/ml)、TNF-α (17.291±1.708～21.159±2.151pg/ml)、IL-1β(11.861±5.179～22.767±7.191pg/ml)、 IL-8(19.489±4.378～60.185±9.71]pg/ml)浓度较对照组显著增高(P0.05)。且HSF2血清浓度与UC-DAI评分(r=0.78), TNF-α (r=0.77)、 IL-β (r=0.73)、 IL-8(r=0.85)浓度呈正相关性(P0.001)。结论：HSF2与TNF-α、IL-1β、IL-8在溃疡性结肠炎结肠黏膜组织及血清中的表达均增加,且HSF2与UC-DAI评分、TNF-α、IL-1β、IL-8的表达具有正相关性,提示HSF2可能作为一项新的评估UC炎症活动程度的指标。
[Abstract]:Background : ulcerative colitis ( UC ) is a non - specific chronic inflammatory disease of the intestine . The pathogenesis of UC is not clear . The disease is seen in any age , but the expression of HSF2 in the intestinal mucosa of UC patients is increased . The results suggest that HSF2 can be used as a new index to assess the degree of UC inflammation .

Objective : To evaluate the transcription and translation levels of HSF2 and pro - inflammatory cytokines ( TNF - 伪 , IL - 1尾 , IL - 8 ) in colonic mucosa and serum of patients with UC and to evaluate the relationship between HSF2 and the severity of UC and its correlation with the expression of pro - inflammatory cytokines .

Methods : The expression of HSF2 , TNF - 伪 , IL - 1尾 , IL - 8 in colonic mucosa was determined by real - time fluorescence quantitative polymerase chain reaction ( ELISA ) .

Results : There were 20 cases of intestinal mucosal tissue samples collected from patients with UC active phase , 5 in control group , 60 in UC patients and 20 in control group .

1 . The expression of HSF2 ( 1.300 卤 0.107 ~ 2.204 卤 1.190folds ) , TNF - 伪 ( 6.278 卤 1.791 - 19.228 卤 4.383folds ) , IL - 1尾 ( 48.906 卤 13.716 ~ 212.894 卤 29.692folds ) and IL - 8 ( 27.489 卤 4.549 ~ 124.732 卤 26.084folds ) mRNA in UC patients were significantly higher than those in the control group ( P0.05 ) .

The levels of IL - 1尾 ( r = 0.78 ) , TNF - 伪 ( r = 0.77 ) , IL - 尾 ( r = 0.73 ) and IL - 8 ( r = 0.85 ) were positively correlated ( P0.001 ) .

Conclusion : The expression of HSF2 and TNF - 伪 , IL - 1尾 , IL - 8 in colonic mucosa and serum of ulcerative colitis increased , and HSF2 was positively correlated with the expression of UC - DAI , TNF - 伪 , IL - 1尾 , IL - 8 , suggesting that HSF2 might be a new index to assess the degree of UC inflammation .

【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62

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