维生素D水平与溃疡性结肠炎患者TLR4/NF-κB信号通路及疾病活动度的相关性分析

Correlation analysis of vitamin D level with TLR4/NF-κB signaling pathway and disease activity in patients with ulcerative colitis

摘要:

目的 研究维生素D水平与溃疡性结肠炎（UC）患者Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路及疾病活动度的相关性。方法 选取2020年1月—2021年12月胜利油田中心医院消化内科门诊收治的100例UC患者为观察组，另选取同期该院健康体检中心50例体检正常者为对照组。比较两组的血清红细胞沉降率（ESR）、C反应蛋白（CRP）、粪便钙卫蛋白（FC）、TLR4、NF-κB、25-羟维生素D₃［25（OH）D₃］；绘制受试者工作特征（ROC）曲线分析ESR、CRP、FC、TLR4、NF-κB、25（OH）D₃对UC的诊断价值。根据25（OH）D₃水平将观察组患者分为维生素D充足组［25（OH）D₃≥ 20 ng/mL］20例、维生素D不足组［10 ng/mL≤ 25（OH）D₃< 20 ng/mL］25例及维生素D缺乏组［25（OH）D₃< 10 ng/mL］55例；比较3组的ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量；采用Person相关系数分析ESR、CRP、FC、TLR4、NF-κB与25（OH）D₃的相关性。通过改良Mayo评分评估疾病活动度，分为临床缓解组（改良Mayo评分≤ 2分）20例、轻度组（改良Mayo评分3～5分）32例、中度组（改良Mayo评分6～10分）33例及重度组（改良Mayo评分≥ 11分）15例；比较4组的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB mRNA相对表达量；采用Spearman相关系数分析ESR、CRP、FC、TLR4、NF-κB、25（OH）D₃与疾病活动度的相关性。结果 观察组ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量高于对照组（P <0.05），25（OH）D₃水平低于对照组（P <0.05）；ROC曲线分析结果显示，ESR≥ 19.814 mm/h、CRP ≥ 10.758 mg/L、FC ≥ 103.354 μg/g、25（OH）D₃ ≤ 18.035 ng/mL、TLR4 ≥ 1.515、NF-κB ≥ 1.426时，其诊断UC的曲线下面积（AUC）分别为0.840（95% CI：0.769，0.910）、0.790（95% CI：0.712，0.869）、0.807（95% CI：0.729，0.885）、0.862（95% CI：0.800，0.935）、0.843（95% CI：0.776，0.910）、0.858（95% CI：0.790，0.926），敏感性分别为81.0%（95% CI：0.715，0.925）、78.0%（95% CI：0.725，0.830）、81.0%（95% CI：0.774，0.823）、85.0%（95% CI：0.704，0.937）、82.0%（95% CI：0.750，0.912）、88.0%（95% CI：0.764，0.965），特异性分别为84.0%（95% CI：0.628，0.972）、84.0%（95% CI：0.705，0.971）、82.0%（95% CI：0.659，0.864）、86.0%（95% CI：0.769，0.936）、84.0%（95% CI：0.726，0.936）、84.0%（95% CI：0.751，0.981）。维生素D充足组、维生素D不足组的ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量低于维生素D缺乏组（P <0.05）；临床缓解组、轻度组、中度组ESR、CRP、FC及TLR4、NF-κB mRNA相对表达量低于重度组（P <0.05），25（OH）D₃高于重度组（P <0.05）；ESR、CRP、FC、TLR4、NF-κB与疾病活动度呈正相关（P <0.05）；25（OH）D₃与疾病活动度呈负相关（P <0.05）。结论 UC患者的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB表达与健康人群有显著差异，不同25（OH）D₃水平UC患者的ESR、CRP、FC及TLR4、NF-κB表达均有差异，不同疾病活动度UC患者的ESR、CRP、FC、25（OH）D₃及TLR4、NF-κB表达也存在差异。25（OH）D₃检测可用于UC患者的临床营养治疗及长期随访管理中，通过补充维生素D提升UC治疗效果。

Abstract:

Objective To investigate the correlation between vitamin D levels and toll-like receptor 4 (TLR4) / nuclear factor-κB (NF-κB) signaling pathway and disease activity in patients with ulcerative colitis (UC).Methods From January 2020 to December 2021, 100 patients with UC admitted to the Department of Gastroenterology Shengli Oilfield Central Hospital were selected as the observation group, and 50 patients with normal physical examination in the health examination center of the hospital during the same period were selected as the control group. The serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal caltroverin (FC), TLR4, NF-κB, 25-hydroxyvitamin D₃[25(OH)D₃] of the two groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of ESR, CRP, FC, TLR4, NF-κB, and 25(OH)D₃ for UC. According to 25(OH)D₃ levels, observation group was divided into vitamin D sufficient group [25(OH)D₃ ≥ 20 ng/mL, n = 20], vitamin D deficiency group [10 ng/mL ≤ 25(OH)D₃ < 20 ng/mL, n = 25] and vitamin D deficiency group [25(OH)D₃ < 10 ng/mL, n = 55]; the mRNA expression levels of ESR, CRP, FC, TLR4, and NF-κB in the three groups were compared. Person correlation coefficient was used to analyze the correlation between ESR, CRP, FC, TLR4, NF-κB, and 25(OH)D₃. Disease activity was evaluated by modified Mayo score, which was divided into clinical remission group (modified Mayo score ≤ 2, n = 20), mild group (modified Mayo score 3 to 5, n = 32), moderate group (modified Mayo score 6 to 10, n = 33) and severe group (modified Mayo score ≥ 11, n = 15). The mRNA expression levels of ESR, CRP, FC, 25(OH)D₃, TLR4 and NF-κB in 4 groups were compared. Spearman correlation coefficient was used to analyze the correlation between ESR, CRP, FC, TLR4, NF-κB, 25(OH)D₃ and disease activity.Results Observation group ESR, CRP, FC, TLR4, NF- κB mRNA the relative expression level was higher than that of the control group (P < 0.05), and the level of 25(OH)D₃ was lower than that of the control group (P < 0.05); ROC curve analysis results showed that ESR ≥ 19.814 mm/h, CRP ≥ 10.758 mg/L, FC ≥ 103.354 μg/g, 25(OH)D₃ ≤ 18.035 ng/mL, TLR4 ≥ 1.515, NF-κB ≥ 1.426; the area under the curve (AUC) for the diagnosis of UC were 0.840 (95% CI: 0.769, 0.910), 0.790 (95% CI: 0.712, 0.869), 0.807 (95% CI: 0.729, 0.885), 0.862 (95% CI: 0.800, 0.935), 0.843 (95% CI: 0.776, 0.910), and 0.858 (95% CI: 0.790, 0.926); the sensitivity were 81.0% (95% CI: 0.715, 0.925) and 78.0% (95% CI: 0.725, 0.830), 81.0% (95% CI: 0.774, 0.823), 85.0% (95% CI: 0.704, 0.937), 82.0% (95% CI: 0.750, 0.912), 88.0% (95% CI: 0.764, 0.965); the specificity was 84.0% (95% CI: 0.628, 0.972), 84.0% (95% CI: 0.705, 0.971), 82.0% (95% CI: 0.659, 0.864), 86.0% (95% CI: 0.769, 0.936), 84.0% (95% CI: 0.726, 0.936), and 84.0% (95% CI: 0.751, 0.981). The relative expression levels of ESR, CRP, FC, TLR4, and NF-κB mRNA in vitamin D sufficient group and vitamin D deficiency group were lower than those in vitamin D deficiency group (P < 0.05). The relative expression levels of ESR, CRP, FC, TLR4, and NF-κB mRNA in clinical remission, mild and moderate groups were lower than those in severe group (P < 0.05), and 25(OH)D₃ was higher than those in severe group (P < 0.05). ESR, CRP, FC, TLR4, and NF-κB were positively correlated with disease activity (P < 0.05). 25(OH)D₃ was negatively correlated with disease activity (P < 0.05).Conclusion The expressions of ESR, CRP, FC, 25 (OH)D₃, TLR4, and NF-κB in UC patients were significantly different from those of healthy people, and the expressions of ESR, CRP, FC, TLR4, and NF-κB in UC patients with different 25(OH)D₃ levels were different. The expressions of ESR, CRP, FC, 25(OH)D₃, TLR4, and NF-κB were also different in UC patients with different disease activity. Therefore, 25(OH)D₃ detection can be used in clinical nutritional therapy and long-term follow-up management of UC patients, and vitamin D supplementation can improve the therapeutic effect of UC.