METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention.
RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001).
CONCLUSIONS: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.
方法:在目前的随机安慰剂对照试验中,36名活动性UC患者随机分为丁酸钠(600mg/kg)或安慰剂,为期12周。在这项研究中,通过实时聚合酶链反应(qPCR)评估了昼夜节律基因(CRY1,CRY2,PER1,PER2,BMAL1和CLOCK)在全血中的表达。基因表达变化表示为相对于基线的表达的倍数变化(2^-ΔΔCT)。采用酶联免疫吸附法(ELIZA)检测粪便钙卫蛋白和血清超敏C反应蛋白(hs-CRP)水平。此外,干预前后分别采用匹兹堡睡眠质量指数(PSQI)和炎症性肠病问卷-9(IBDQ-9)对患者的睡眠质量和IBD生活质量(QoL)进行评估。
结果:结果表明,与安慰剂相比,丁酸钠的补充显着降低了钙卫蛋白的水平(-133.82±155.62vs.51.58±95.57,P值<0.001)和hs-CRP(-0.36(-1.57,-0.05)vs.0.48(-0.09-4.77),P值<0.001),并上调CRY1的倍数变化表达(2.22±1.59vs.0.63±0.49,P值<0.001),CRY2(2.15±1.26vs.0.93±0.80,P值=0.001),PER1(1.86±1.77vs.0.65±0.48,P值=0.005),BMAL1(1.85±0.97vs.0.86±0.63,P值=0.003)。此外,丁酸钠可改善睡眠质量(PSQI评分:-2.94±3.50vs.1.16±3.61,P值<0.001)和QoL(IBDQ-9:17.00±11.36vs.-3.50±6.87,P值<0.001)。
结论:丁酸酯可能是活动期UC患者的一种有效的辅助治疗方法,通过减少炎症的生物标志物,生物钟基因上调,改善睡眠质量和生活质量。