溃疡性结肠炎白细胞介素6异常表达与基因甲基化的关系

摘要

目的 探讨UC患者IL-6的异常表达与基因甲基化的关系,明确表观遗传学在UC中的作用机制.方法 选取2017年3月至2018年3月天津医科大学总医院消化科收治的UC患者59例,另选取同期健康体格检查者58名为健康对照.收集UC患者和健康对照者肠黏膜和血清标本,检测DNA甲基转移酶(DNMT)的活性、IL-6基因启动子区CpG位点的甲基化水平和IL-6的表达水平.采用卡方检验和t检验进行统计学分析.结果 UC组和健康对照组分别有24、30和21、20例完成IL-6基因启动子区甲基化水平和IL-6表达水平的检测.UC组结肠黏膜组织中DNMT活性低于健康对照组[(16.48±6.17) OD·h-1·mg-1比(62.48 ±33.88) OD·h-1·mg-1],差异有统计学意义(t=3.707,P＜0.05).UC组IL-6基因启动子区甲基化、部分甲基化、非甲基化比例分别为31.2％ (15/48)、50.0％(24/48)、18.8％ (9/48),健康对照组分别为58.3％ (35/60)、21.7％ (13/60)、20.0％ (12/60),两组比较差异有统计学意义(x2=10.495,P＜0.05).UC组结肠黏膜IL-6阳性表达率高于健康对照组[100.0％(21/21)比25.0％ (5/20)],差异有统计学意义(x2=24.837,P＜0.05).UC组血清IL-6水平高于健康对照组[(1 075.02 ±661.95) ng/L比(583.43 ±425.10) ng/L],差异有统计学意义(t=3.245,P＜0.05).结论 UC患者肠黏膜DNMT活性降低可能使IL-6基因启动子区甲基化水平降低,从而导致IL-6在肠黏膜和血清的表达水平升高,参与UC的炎症过程.%Objective To investigate the relationship between aberrant expression of interleukin 6 (IL-6) and gene methylation in patients with ulcerative colitis (UC),and to clarify the mechanism of epigenetics in UC.Methods From March 2017 to March 2018,a total of 59 UC patients admitted to the Department of Gastroenterology,General Hospital Affiliated to Tianjin Medical University were enrolled,and at the same time 58 normal individuals who received health checkups were selected as healthy controls.Blood samples and colonic mucosa specimens of UC group and healthy control group were collected.DNA methyltransferase (DNMT) activity,methylation level of CpG locus in IL-6 promoter region and expression level of IL-6 were detected.Chi-square test and student's t test were performed for statistical analysis.Results The methylation level and IL-6 expression level examination were completed in 24 and 30 cases of UC group,respectively;which were detected in 21 and 20 cases of healthy control group,respectively.The activity of DNMT of UC group was significantly lower than that of healthy control group ((16.48 ± 6.17) OD · h-1 · mg-1 vs.(62.48 ± 33.88) OD · h-1 ·mg-1),and the difference was statistically significant (t =3.707,P ＜ 0.05).The ratios of methylation,partial methylation and non-methylation of UC group were 31.2％ (15/48),50.0％ (24/48) and 18.8％ (9/48),respectively,and those of healthy control group were 58.3％ (35/60),21.7％ (13/60) and 20.0％ (12/60),and the difference between the two groups was statistically significant (x2 =10.495,P ＜ 0.05).The positive expression rate of IL-6 in intestinal mucosa of UC group was higher than that of healthy control group (100.0％,21/21 vs.25.0％,5/20),and the difference was statistically significant (x2 =24.837,P ＜0.05).The serum IL-6 level of UC group was higher than that of healthy control group ((1 075.02 ±661.95) ng/L vs.(583.43 ± 425.10) ng/L),and the difference was statistically significant (t =3.245,P ＜ 0.05).Conclusion The decrease of DNMT activity in the intestinal mucosa of UC patients may reduce the methylation level of IL-6 gene promoter region,which is correlated with the increased level of IL-6 expression in the intestinal mucosa and serum,and involve in the inflammatory process of UC.