雌激素对溃疡性结肠炎患者NF-κB、IL-6及NO表达的影响

Effect of estrogen on the expression of NF- kappa B, IL-6 and NO in patients with ulcerative colitis

目的探讨雌激素对于溃疡性结肠炎患者核因子κB(nuclear factor κB,NF-κB)、白细胞介素6(interleukin-6,IL-6)以及一氧化氮(nitric oxide,NO)表达的影响。方法选取2015年2月至2018年1月收治我院的溃疡性结肠炎患者110例,按性别分成男性组(47例)和女性组(63例)。采用免疫组织化学法、酶联免疫吸附法以及硝酸还原法对两组患者的NF-κB P65、IL-6以及NO等炎症指标表达水平进行测定。另外收集两组患者的病变肠粘膜以及周围正常肠粘膜组织并制作石蜡组织芯片,行免疫组织化学染色,分析并比较雌激素受体β1(estrogen receptor β1,ERβ1)、雌激素受体α(estrogen receptor α,ERα)、雄激素受体(androgen receptor,AR)以及孕激素受体(progesterone receptor,PR)的表达情况。结果①男性组患者的NF-κB P65、IL-6的表达水平均显著高于女性组患者,差异具有统计学意义(t值分别为19.730,7.204;P值均<0.05);②男性组患者的NO、白细胞(white blood cell,WBC)以及血小板(platelet,PLT)水平均明显高于女性组患者,差异具有统计学意义(t值分别为8.683,8.015,5.237;P值均<0.05);③正常肠粘膜组织的ERβ1的阳性率为84.55%(93/110),显著高于病变肠粘膜组织的ERβ1阳性率63.64%(70/110),差异有统计学意义(χ2=12.526,P<0.05);男性组患者的病变组织中的ERβ1的阳性率为76.60%(36/47),显著高于女性患者病变组织中的ERβ1的阳性率53.97%(34/63),差异有统计学意义(χ2=5.956,P<0.05);并且女性组中绝经后期患者病变组织中的ERβ1的阳性率为80.00%(36/45),显著高于绝经前期患者病变组织中的的ERβ1的阳性率38.89%(7/18),差异有统计学意义(χ2=10.029,P<0.05)。ERα、AR和PR在两组患者的病变组织以及正常黏膜中的表达均为阴性。结论雌激素能够通过与ERβ1受体结合,抑制P38/MAPK通路,从而减少溃疡性结肠炎患者体内的NF-κB P65、IL-6以及NO水平的表达,对溃疡性结肠炎疾病的疾病发展起到抑制作用。

Objective To investigate the effect of estrogen on the expression of nuclear factor κB (NF-κB),interleukin-6 (IL-6) and nitric oxide (NO) in patients with ulcerative colitis. Methods Total of 110 patients of ulcerative colitis in our hospital from February 2015 to January 2018 were selected and divided into male(47) and female(63)groups.The immunohistochemistry,double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and enzyme labeling were used to determine the expression levels of NF-κB P65,IL-6,and NO in the subjects.The intestinal mucosa of the patients and the normal intestinal mucosal tissue specimens were collected.Tissue was fixed,embedded in paraffin,and subjected to microarray analysis.Immunohistochemistry staining was performed to analyze the expression of estrogen receptor β1(ERβ1),estrogen receptor α (ERα),androgen receptor (AR),and progesterone receptor (PR). Results The expression level of NF- kappa B p65 and IL-6 in the male patients was significantly higher than that in the female patients (t values were 19.730,7.204 respectively;all P values were <0.05).The levels of NO,white blood cell(WBC),and platelet (PLT) in male patients were significantly higher than those in female patients (t values were 8.683,8.015,5.237 respectively;all P values were < 0.05).The positive rate of ERβ1 in normal intestinal mucosa was 84.55% (93/110),which was significantly higher than the positive rate of ERβ1 (70/110) in the intestinal mucosa of the lesion (70/110) (χ2=12.526,P<0.05).The positive rate of ERβ1 in the pathological tissue of the male patients was 76.60% (36/47),which was significantly higher than the that of diseased tissue in the female patients [53.97% (34/63)](χ2=5.956,P<0.05).The positive rate of ERβ1 in the pathological tissue of postmenopausal patients was 80% (36/45),which was significantly higher than the positive rate of ERβ1 in the pathological tissue of premenopausal patients [38.89% (7/18)](χ2=10.029,P=0.002).The expressions of ER,AR,and PR were all negative in all patients. Conclusion Estrogen can inhibit the expression of NF-κB P65,IL-6,and NO in patients with ulcerative colitis by binding to ER beta 1 receptor and inhibiting the P38/MAPK pathway.Thus,estrogen may inhibit the development of ulcerative colitis.