血清HIF-1α对溃疡性结肠炎患者疾病活动性及黏膜愈合评估价值的研究

Evaluation value of serum HIF-1α in disease activity and mucosal healing in ulcerative colitis patients

目的:探讨血清低氧诱导因子-1α(HIF-1α)表达与溃疡性结肠炎(UC)疾病活动性及其黏膜愈合的关系。方法:以2017年9月—2022年3月收治的82例UC患者及30例同期健康体检者(对照组)为研究对象。采用ELISA法测定血清HIF-1α、IL-1β、IL-6、IL-17、C反应蛋白(CRP)水平,氯化硝基四氮唑蓝(NBT)法检测超氧化物歧化酶(SOD)含量,硫代巴比妥酸(TBA)法检测丙二醛(MDA)含量;分析HIF-1α表达与UC患者病情活动性、内镜分级、上述各指标及临床疗效的关系;采用受试者工作特征曲线(ROC)评估HIF-1α、炎症因子、CRP、氧化应激指标对内镜下黏膜愈合的预测价值。结果:活动期组UC患者血清HIF-1α水平较缓解期组和对照组明显升高,且HIF-1α在不同临床严重程度、内镜表现分级间表达差异有统计学意义,并与其呈显著正相关(r=0.812、0.719,P<0.05);随着UC临床严重程度增加,IL-1β、IL-6、IL-17及CRP水平增加,HIF-1α表达与其呈正相关(r=0.527、0.476、0.612、0.571,P<0.05);SOD表达下降,HIF-1α表达与其呈负相关(r=-0.497,P<0.05);MDA表达增加,HIF-1α表达与其呈正相关(r=0.502,P<0.05);ROC曲线结果显示,SOD、MDA、IL-1β、IL-17、IL-6、CRP、HIF-1α预测的曲线下面积(AUC)分别为0.648、0.761、0.718、0.731、0.795、0.804、0.874,具有一定的区分度。HIF-1α的AUC大于其他指标预测的AUC,区分度更好。HIF-1α在UC患者黏膜愈合预测中具有较高的灵敏度和特异度。结论:血清HIF-1α水平与UC疾病活动性及黏膜愈合具有相关性,血清HIF-1α表达水平随UC严重程度增加而增加,并且HIF-1α表达量与机体炎症反应、氧化应激反应功能紊乱程度具有相关性。血清HIF-1α在UC患者疾病活动性及黏膜愈合评估上具有重要意义。

Objective:To investigate the relationship between the expression of serum hypoxia inducible factor-1α(HIF-1α)and the disease activity and mucosal healing in ulcerative colitis(UC).Methods:Eighty-two patients with UC and 30 healthy subjects in the same period(control group)were admitted from September 2017 to March 2022.Determination of serum HIF-1α,IL-1β,IL-6,IL-17 and C-reactive protein(CRP)by ELISA.Determination of superoxide dismutase(SOD)by nitroblue tetrazolium(NBT)method.Determination of malondialdehyde(MDA)by thiobarbituric acid(TBA).To analyze the relationship between the expression of HIF-1α and disease activity,endoscopic grading,above-mentioned indexes and clinical efficacy in patients with UC.The value of HIF-1α,inflammatory cytokines,CRP and oxidative stress in predicting endoscopic mucosal healing was evaluated by receiver operating characteristic(ROC)curve.Results:The level of serum HIF-1α in active UC patients was significantly higher than that in remission group and control group,and the expression of HIF-1αwas significantly different among different clinical severity and endoscopic manifestation grades,and positively correlated with it(r=0.812,0.719,P<0.05).With the increase of clinical severity of UC,the levels of IL-1β,IL-6,IL-17 and CRP increased,and the expression of HIF-1α was positively correlated with it(r=0.527,0.476,0.612,0.571,P<0.05);the expression of SOD decreased,and the expression of HIF-1α negatively correlated with it(r=-0.497,P<0.05);the expression of MDA increased,and the expression of HIF-1α positively correlated with it(r=0.502,P<0.05).The results of ROC curve show that the area under the curve(AUC)predicted by SOD,MDA,IL-1β,IL-17,IL-6,CRP and HIF-1α is 0.648,0.761,0.718,0.731,0.795,0.804 and 0.874 respectively,which has a certain degree of distinction.The AUC of HIF-1α is higher than that of AUC predicted by other indexes,and the degree of differentiation is better.HIF-1α has high sensitivity and specificity in predicting mucosal healing in patients with UC.Conclusion:The level of serum HIF-1α was correlated with the activity of UC disease and mucosal healing,and increased with the increase of the severity of UC,and the expression of HIF-1α was correlated with the degree of inflammation and oxidative stress.Serum HIF-1α plays an important role in the evaluation of disease activity and mucosal healing in patients with UC.