Efficacy of Saccharomyces boulardii combined with sulfasalazine suppository in the treatment of rectal ulcerative colitis and its effect on intestinal flora and intestinal mucosal barrier function
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摘要: 目的 探讨布拉氏酵母菌联合柳氮磺吡啶栓治疗直肠型溃疡性结肠炎(UC)的临床疗效以及其对患者肠道菌群和肠黏膜屏障功能的影响。方法 选取2019年1月—2020年10月廊坊市人民医院收治的94例直肠型UC患者，使用随机数字表法分成观察组与对照组各47例。对照组给予柳氮磺吡啶栓治疗，在此基础上，观察组口服布拉氏酵母菌散治疗。所有对象均连续治疗8周后观察2组疗效及退热时间。比较治疗前后2组主要症状(腹泻、脓血便、腹痛)评分、改良Baron内镜评分、炎症性肠病问卷(IBDQ)总分、粪便中肠道菌群(双歧杆菌、乳酸杆菌、肠球菌、肠杆菌)数量及肠黏膜屏障功能指标[尿中乳果糖与甘露醇比值(L/M)和血清D-乳酸(D-LA)、二胺氧化酶(DAO)、内毒素脂多糖(LPS)水平]。统计2组药物不良反应情况。结果 所有对象均顺利完成本次研究，无脱落病例。观察组总有效率[93.62%(44/47)]显著高于对照组[76.60%(36/47)，P< 0.05]。观察组退热时间较对照组显著缩短(P< 0.05)。2组治疗后腹泻、脓血便和腹痛评分均显著低于治疗前(P< 0.05)；且治疗后，观察组腹泻、脓血便和腹痛评分均显著低于对照组(P< 0.05)。2组治疗后改良Baron内镜评分均显著低于治疗前(P< 0.05)，IBDQ总分均显著高于治疗前(P< 0.05)；但均以观察组的改善更显著(P< 0.05)。2组治疗后粪便中双歧杆菌、乳酸杆菌数量较治疗前均显著增加(P< 0.05)，粪便中肠球菌、肠杆菌数量较治疗前均显著减少(P< 0.05)；且治疗后，观察组对肠道菌群失调的改善作用较对照组更显著(P< 0.05)。与治疗前比较，2组治疗后尿中L/M及血清D-LA、DAO、LPS浓度均显著降低(P< 0.05)；且治疗后，观察组对尿中L/M及血清D-LA、DAO、LPS水平的降低作用较对照组更显著(P< 0.05)。所有对象均未见明显药物不良反应。结论 布拉氏酵母菌联合柳氮磺吡啶栓治疗直肠型UC的整体疗效确切，能安全有效地缩短患者退热时间，促进腹泻、脓血便和腹痛的缓解，减轻肠黏膜炎症状态，提高生活质量，其作用可能与其显著纠正肠道菌群失衡、改善肠黏膜屏障功能有关。Abstract: Objective To investigate the clinical efficacy of Saccharomyces boulardii combined with sulfasalazine suppository in the treatment of rectal ulcerative colitis(UC) and its effect on intestinal flora and intestinal mucosal barrier function.Methods Ninety-four patients with rectal UC treated in our hospital from January 2019 to October 2020 were randomly divided into observation group and control group. The control group was treated with sulfasalazine suppository. On this basis, the observation group was treated with Saccharomyces boulardii powder. After 8 weeks of continuous treatment, the curative effect and antipyretic time of the two groups were observed. The scores of main symptoms, modified Baron endoscopy, the total score of inflammatory bowel disease questionnaire(IBDQ), the number of intestinal flora(Bifidobacterium, Lactobacillus, Enterococcus and Enterobacter) in feces and the function index of intestinal mucosal barrier(the ratio of lactulose to mannitol in urine[L/M] and the levels of serum D-lactic acid[D-LA], diamine oxidase[DAO] and endotoxin lipopolysaccharide[LPS]). Compared between two groups, the side effects of the two groups were counted.Results The total effective rate of the observation group(93.6%[44/47])was significantly higher than that of the control group(76.6%[36/47],P< 0.05). The antipyretic time of the observation group was significantly shorter than that of the control group(P< 0.05); the scores of main symptoms(diarrhea, purulent bloody stool and abdominal pain) in the two groups after treatment were significantly lower than those before treatment(P< 0.05), but the decrease in the observation group was more significant(P< 0.05). The scores of modified Baron endoscopy in the two groups after treatment were significantly lower than those before treatment(P< 0.05), and the total IBDQ scores were significantly higher than those before treatment(P< 0.05), but the improvement in the observation group was more significant(P< 0.05). The numbers of bifidobacteria and Lactobacillus in feces in the two groups after treatment were significantly higher than those before treatment(P< 0.05), the number of Enterococcus and Enterobacter in feces decreased significantly compared with that before treatment(P< 0.05), and the improvement of intestinal flora imbalance in the observation group was more significant than that in the control group(P< 0.05). Compared with that before treatment, the concentrations of L/M in urine and D-LA, DAO and LPS in serum decreased significantly in the two groups after treatment(P< 0.05).And after treatment, the observation group had more significant effects on the reduction of L/M in urine and the levels of D-LA, DAO and LPS in serum than the control group(P< 0.05).Conclusion Saccharomyces boulardii combined with sulfasalazine suppository in the treatment of rectal UC has a definite overall effect. It can safely and effectively alleviate the symptoms of patients, reduce the inflammatory state of intestinal mucosa and improve the quality of life. Its effect may be related to significantly correcting the imbalance of intestinal flora and improving the function of intestinal mucosal barrier.
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表 1 2组临床疗效比较
例(%) 组别 例数 完全缓解 有效 无效 总有效 观察组 47 19(40.43) 25(53.19) 3(6.38) 44(93.62)1) 对照组 47 15(31.91) 21(44.68) 11(23.40) 36(76.60) 与对照组比较，1)P < 0.05。 
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表 2 2组退热时间及主要症状评分比较
X±S 组别 例数 退热时间/d 腹泻/分 脓血便/分 腹痛/分 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 47 4.22±0.982) 5.05±0.67 2.62±0.351)2) 3.63±0.92 1.83±0.381)2) 4.77±1.05 2.37±0.481)2) 对照组 47 8.45±1.73 4.92±0.72 3.05±0.591) 3.78±0.83 2.56±0.541) 4.84±0.89 3.16±0.611) 与同组治疗前比较，1)P < 0.05；与对照组比较，2)P < 0.05。
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表 3 2组改良Baron内镜评分和IBDQ总分比较
分，X±S 组别 例数 改良Baron内镜评分 IBDQ总分 治疗前 治疗后 治疗前 治疗后 观察组 47 1.61±0.36 0.66±0.171)2) 114.84±12.33 186.73±20.851)2) 对照组 47 1.57±0.28 1.05±0.311) 111.69±13.28 153.16±17.241) 与同组内治疗前比较，1)P < 0.05；与对照组比较，2)P < 0.05。
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表 4 2组肠道菌群数量比较
lgCFU/g，X±S 组别 例数 时间 双歧杆菌 乳酸杆菌 肠球菌 肠杆菌 观察组 47 治疗前 6.34±0.55 7.02±0.58 8.25±0.61 8.16±0.62 治疗后 8.98±0.761)2) 9.15±0.781)2) 4.76±0.371)2) 4.93±0.421)2) 对照组 47 治疗前 6.28±0.57 6.94±0.69 8.41±0.59 8.07±0.63 治疗后 7.75±0.641) 8.37±0.711) 6.28±0.491) 6.64±0.541) 与同组治疗前比较，1)P < 0.05；与对照组比较，2)P < 0.05。
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表 5 2组肠黏膜屏障功能指标比较X±S
组别 例数 时间 L/M D-LA/(U·L-1) DAO/(mg·L-1) LPS/(pg·mL-1) 观察组 47 治疗前 0.038±0.009 18.53±4.14 11.37±3.06 87.34±16.28 治疗后 0.028±0.0031)2) 6.77±1.781)2) 4.79±1.251)2) 16.47±3.081)2) 对照组 47 治疗前 0.040±0.007 19.12±4.51 12.18±2.97 91.41±17.31 治疗后 0.032±0.0061) 10.27±3.051) 7.92±2.031) 27.75±5.121) 与同组治疗前比较，1)P < 0.05；与对照组比较，2)P < 0.05。
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