检测炎症性肠病患者血清铜/锌比值的临床意义

Clinical significance of the ratio of serum copper to zinc in patients with inflammatory bowel disease

目的探讨炎症性肠病(IBD)患者血清铜、锌水平及其比值在评估疾病活动度中的应用价值。方法采用前瞻性随机直抽样法,选择2019年3月至2020年4月在安徽医科大学第一附属医院消化内科住院的IBD患者200例,其中克罗恩病患者100例(克罗恩病组),溃疡性结肠炎(UC)患者100例(UC组),分别采用克罗恩病疾病活动指数(CDAI)和改良Mayo评分评估克罗恩病和UC患者的疾病活动度;另选择100名同期健康体检无异常者作为健康对照组。采用原子吸收光谱法测定健康对照组、克罗恩病组和UC组的血清铜、锌的水平,并比较3组间的血清铜、锌的水平及其比值;比较不同疾病活动度克罗恩病和UC患者的血清铜/锌比值,并分析血清铜/锌比值与IBD活动度相关指标[包括粪钙防卫蛋白(FC)、C反应蛋白(CRP)、红细胞沉降率(ESR)、CDAI和Mayo评分]的相关性;绘制受试者操作特征曲线分析血清铜/锌比值、CRP、ESR预测IBD患者疾病活动度的价值。统计学方法采用独立样本t检验、最小显著性差异-t检验和Pearson相关分析。结果克罗恩病组和UC组患者的血清铜水平和血清铜/锌比值均高于健康对照组,血清锌水平均低于健康对照组[(32.27±7.69)和(29.80±9.68)mol/L比(20.16±6.67)mol/L、2.81±1.57和2.29±1.09比0.68±0.36、(14.64±7.11)和(15.65±8.17)mol/L比(34.29±16.40)mol/L],差异均有统计学意义(t=2.81、5.87、1.47、7.21、1.73、2.56,P均<0.05)。克罗恩病患者中,缓解期(29例)、轻度活动期(23例)、中度活动期(30例)、重度活动期(18例)患者的血清铜/锌比值分别为2.61±1.43、2.75±1.35、3.15±2.37、4.17±1.77,轻度活动期、中度活动期、重度活动期患者的血清铜/锌比值均高于缓解期患者,差异均有统计学意义(t=3.41、7.92、5.84,P均<0.05)。轻度活动期与中度活动期、重度活动期,中度活动期与重度活动期患者的血清铜/锌比值比较差异均有统计学意义(t=5.82、6.23、3.45,P均<0.05)。UC患者中,缓解期(10例)、轻度活动期(30例)、中度活动期(45例)、重度活动期(15例)患者的血清铜/锌比值分别为1.52±0.44、1.74±0.58、2.38±0.83、3.80±1.19,中度活动期患者的血清铜/锌比值高于缓解期和轻度活动期患者,重度活动期患者的血清铜/锌比值高于缓解期、轻度活动期和中度活动期患者,差异均有统计学意义(t=7.92、5.83、3.21、9.54、2.83,P均<0.05);缓解期患者的血清铜/锌比值与轻度活动期患者比较差异无统计学意义(P>0.05)。CD患者的血清铜/锌比值与FC、CRP均呈正相关(r=0.697、0.586,P=0.014、0.001),与ESR、CDAI评分无关(P均>0.05);UC患者的血清铜/锌比值与FC、ESR、Mayo评分均呈正相关(r=0.488、0.452、0.331,P=0.001、P<0.01、P=0.041),与CRP无关(P>0.05)。血清铜/锌比值、CRP和ESR诊断CD活动度的临界值分别为1.76、8 mg/L和20 mm/1 h,其中ESR对诊断CD活动度的效能最高,曲线下面积(AUC)值为0.830,灵敏度和特异度分别为69.0%和86.2%;血清铜/锌比值、CRP和ESR诊断UC活动度的临界值分别为1.63、8 mg/L和20 mm/1 h,其中血清铜/锌比值对诊断UC活动度的效能最高,AUC值为0.862,灵敏度和特异度分别为73.0%和90.9%。结论血清铜/锌比值与IBD的疾病活动度具有相关性,可能成为判断疾病活动度的新辅助指标。

Objective To explore the serum levels of copper and zinc and the application value of the ratio in assessing disease activity in patients with inflammatory bowel disease(IBD).Methods From March 2019 to April 2020,200 patients with IBD hospitalized at the Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University were selected by prospective random direct sampling method,including 100 patients with Crohn′s disease(CD)and 100 patients with ulcerative colitis(UC).The Crohn′s disease activity index(CDAI)and the modified Mayo score were used to evaluate the disease activity of CD patients and UC patients.In the same period 100 healthy individuals in the routine physical examination were selected as healthy control group.The serum levels of copper and zinc of the healthy control group,the CD group and the UC group were determined by atomic absorption spectrometry.The levels and the ratio of serum copper to zinc of three groups were compared.The ratio of serum copper to zinc of CD patients and UC patients with different disease activity were compared.The correlation between the ratio of serum copper to zinc and IBD activity indexes were analyzed,which included fecal calprotectin(FC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),CDAI and Mayo score.Receiver operating characteristic curve was drawn to analyze the value of the ratio of serum copper to zinc,CRP and ESR in predicting disease activity of patients with IBD.Independent sample t test,least significant difference-t test and Pearson correlation analysis were performed for statistical analysis.Results The serum copper levels and the ratio of serum copper to zinc of the CD group and the UC group were both higher than that of the healthy control group,however the serum zinc levels were lower than that of the healthy control group((32.27±7.69)and(29.80±9.68)mol/L vs.(20.16±6.67)mol/L;2.81±1.57 and 2.29±1.09 vs.0.68±0.36;(14.64±7.11)and(15.65±8.17)mol/L vs.(34.29±16.40)mol/L),and the differences were statistically significant(t=2.81,5.87,1.47,7.21,1.73 and 2.56,all P<0.05).Among CD patients,the the ratio of serum copper to zinc of patients at remission stage(29 cases),mild activity stage(23 cases),moderate activity stage(30 cases)and severe activity stage(18 cases)was 2.61±1.43,2.75±1.35,3.15±2.37 and 4.17±1.77,respectively,and the ratios of serum copper to zinc of patients at mild activity stage,moderate activity stage and severe activity stage were all higher than that of patients at the remission stage,and the differences were statistically significant(t=3.41,7.92 and 5.84,all P<0.05).There were statistically significant differences in the ratios of serum copper to zinc between patients at mild activity stage and moderate activity stage,severe activity stage,and between patients at moderate activity stage and severe activity stage(t=5.82,6.23 and 3.45,all P<0.05).Among UC patients,the ratio of serum copper to zinc of patients at remission stage(10 cases),mild activity stage(30 cases),moderate activity stage(45 cases)and severe activity stage(15 cases)was 1.52±0.44,1.74±0.58,2.38±0.83 and 3.80±1.19,respectively,the ratio of serum copper to zinc of patients at moderate activity stage was higher than that of patients at remission stage and mild activity stage,and the ratio of serum copper to zinc of patients at severe activity stage was higher than those of patients at remission stage,mild activity stage and moderate activity stage,and the differences were statistically significant(t=7.92,5.83,3.21,9.54 and 2.83,all P<0.05).There was no statistically significant difference in serum copper to zinc ratio between patients at remission and at mild activity stage(P>0.05).The ratio of serum copper to zinc of CD patients was positively correlated with FC and CRP(r=0.697 and 0.586,P=0.014 and 0.001),however was not correlated with ESR or CDAI score(both P>0.05).The ratio of serum copper to zinc of UC patients was positively correlated with FC,ESR and Mayo score(r=0.488,0.452 and 0.331,P=0.001,P<0.01 and P=0.041),however was not correlated with CRP(P>0.05).The cut-off value of the ratio of serum copper to zinc,CRP and ESR for the diagnosis of CD activity was 1.76,8 mg/L and 20 mm/1 h,respectively.Among them,ESR was the most effective in the diagnosis of CD activity with an area under the curve(AUC)value of 0.830,and to the sensitivity and specificity was 69.0%and 86.2%,respectively.The cut-off value of the ratio of serum copper to zinc,CRP and ESR for the diagnosis of UC activity was 1.63,8 mg/L and 20 mm/1 h,respectively;among which the the ratio of serum copper to zinc had the highest efficacy in the diagnosis of UC activity,with an AUC value of 0.862,sensitivity and specificity of 73.0%and 90.9%,respectively.Conclusion The the ratio of serum copper to zinc is correlated with the disease activity of IBD,which may become a new auxiliary indicator for the evaluation of disease activity.