Clinical study of Jiedu Huoxue Decoction enema combined with oral Chinese medicine in patients with ulcerative colitis
-
摘要:
目的 观察解毒活血灌肠方联合中药口服治疗溃疡性结肠炎(ulcerative colitis,UC)的疗效并探讨其可能的机制。 方法 选择2016年7月—2018年6月北京中医药大学东直门医院、北京中医药大学第三附属医院的住院及门诊UC患者80例,根据随机数字表法分2组,灌肠组40例采用解毒活血灌肠方联合中药口服治疗,对照组40例仅采用中药口服治疗。采用改良Mayo评分判定临床疗效,观察治疗前后2组患者相关血清炎症因子水平、结肠组织病理评分及血管内皮生长因子(VEGF)、黏膜地址素细胞黏附分子-1(Madcam-1)的表达,有效病例随访2年。 结果 治疗后2组改良Mayo评分均随时间下降(P < 0.05)。治疗2、4周后灌肠组改良Mayo评分[(3.30±0.18)分、(4.30±0.27)分]低于对照组[(4.85±0.45)分、(6.15±0.38)分, 均P < 0.05]。治疗3个月后2组患者血清IL-8、TNF-α、VEGF、Madcam-1水平较治疗前降低(均P < 0.05),灌肠组各炎症因子水平低于对照组(均P < 0.05)。2组患者结肠组织病理评分较前降低(P < 0.01),灌肠组病理评分低于对照组(P < 0.05)。2组患者结肠黏膜VEGF、Madcam-1表达均低于治疗前(均P < 0.05)。有效病例随访2年,灌肠组复发率低于对照组(P < 0.05)。 结论 中药口服治疗溃疡性结肠炎有效,加用灌肠治疗能更快缓解症状,可能通过减少炎症因子释放,从而减轻血管炎症反应,使患者更长时间稳定于缓解期。 Abstract:Objective To evaluate the efficacy of Jiedu Huoxue Decoction enema combined with oral Chinese medicine in treating ulcerative colitis (UC) and explore the possible mechanism of action. Methods Total 80 patients with UC were selected from inpatients and outpatients in Dongzhimen Hospital of the Beijing University of Chinese Medicine and the Third Hospital affiliated Beijing University of Chinese Medicine from July 2016 to June 2018. According to the random number table method, 40 patients in the enema group were treated with Jiedu Huoxue Decoction enema combined with oral Chinese medicine, whereas 40 patients in the control group were treated with oral Chinese medicine only. The modified Mayo score was used to determine the clinical efficacy before and after treatment. The levels of inflammatory cytokine in the serum before and after treatment were determined. The expressions of vascular endothelial growth factor (VEGF) and anti-mucosal addressin cellular adhesion molecule-1 (Madcam-1) in the colon tissue before and after treatment were also observed. Effective telephone follow-up was conducted for 2 years. Results The modified Mayo scores of both groups decreased with time after treatment (P < 0.05). After 2 and 4 weeks of treatment, the improved Mayo scores of the enema group [(3.30±0.18) points and (4.30±0.27) points], were significantly lower than those of the control group [(4.85±0.45) points and (6.15±0.38) points, P < 0.05]. After 3 months of treatment, the serum levels of IL-8, TNF-α, VEGF and Madcam-1 in the two groups were significantly lower than those before treatment (P < 0.05). The serum levels of IL-8, TNF-α, VEGF and Madcam-1 in the enema group were significantly lower than those in the control group (P < 0.05). The expressions of VEGF and Madcam-1 in the colonic mucosa of the two groups were lower than before treatment (P < 0.05). The results of 2-year telephone follow-up showed that the recurrence rate of the enema group was significantly lower than that of the control group (P < 0.05). Conclusion Oral Chinese materia medica is effective in treating UC, whereas enema can relieve symptoms more quickly. It may reduce the release of inflammatory factors, thus reducing vascular inflammation and keeping patients in remission for a longer period. -
Key words:
- Jiedu Huoxue Decoction /
- Ulcerative colitis /
- Efficacy evaluation /
- Enema treatment
-
表 1 2组UC患者一般资料比较
组别 例数 年龄(x ±s,岁) 性别(男/女,例) 病程(x ±s,年) 活动度分级(例) 病变范围(例) 轻 中 重 E1 E2 E3 灌肠组 40 44.73±12.13 20/20 5.82±1.08 15 16 9 14 15 11 对照组 40 42.63±12.17 21/19 6.31±1.13 16 16 8 17 14 9 统计量 0.703a 0.050b 0.309a -0.214c -0.713c P值 0.484 0.823 0.758 0.830 0.476 注:a为t值,b为χ2值,c为Z值。E1为直肠型,E2为左半结肠型,E3为广泛结肠型。 表 2 2组UC患者不同时间改良Mayo评分比较(x ±s,分)
组别 例数 治疗前后 F值 P值 治疗前 治疗2周 治疗4周 治疗3个月 对照组 35 7.15±2.53 6.15±2.40 4.23±1.73 1.13±0.99 11.120 < 0.001 灌肠组 36 7.13±2.91 4.85±2.30 3.30±1.12 0.93±0.92 20.185 < 0.001 t值 0.053 2.470 3.066 0.421 P值 0.395 0.016 0.003 0.352 注:治疗时间与分组存在交互效应,F=2.388,P=0.008。 表 3 2组UC患者治疗前后血清IL-8、TNF-α、VEGF、Madcam-1水平比较(x ±s,pg/mL)
组别 例数 IL-8 t值 P值 TNF-α t值 P值 治疗前 治疗3个月 治疗前 治疗3个月 对照组 35 29.89±20.05 16.67±14.24 3.178 0.002 29.16±22.02 7.66±6.26 5.554 < 0.001 灌肠组 36 34.42±17.83 7.60±3.05 8.895 < 0.001 28.67±22.19 3.91±4.18 6.578 < 0.001 t值 1.008 3.735 0.093 2.976 P值 0.317 < 0.001 0.926 0.004 组别 例数 VEGF t值 P值 Madcam-1 t值 P值 治疗前 治疗3个月 治疗前 治疗3个月 对照组 35 406.50±131.94 162.49±156.12 9.087 < 0.001 189.15±57.68 103.23±41.26 7.168 < 0.001 灌肠组 36 354.91±156.12 113.27±90.98 8.024 < 0.001 150.93±107.71 63.38±26.52 4.375 < 0.001 t值 0.150 2.310 1.856 4.854 P值 0.138 0.024 0.068 < 0.001 注:IL-8为白细胞介素8,TNF-α为肿瘤坏因子α,VEGF为血管内皮生长因子,Madcam-1为黏膜地址素细胞黏附分子-1。 表 4 2组UC患者治疗前后结肠组织病理评分比较(x ±s,分)
组别 例数 治疗前 治疗3个月 t值 P值 对照组 35 3.62±2.02 1.00±0.96 7.417 < 0.001 灌肠组 36 3.90±2.15 0.63±0.63 9.264 < 0.001 t值 0.590 2.066 P值 0.557 0.042 -
[1] SANDS B E, SCHREIBER S, LIRIO R A. Vedolizumab versus adalimumab for moderate-to-severe Ulcerative Colitis[J]. N Engl J Med, 2019, 381(13): 1215-1226. doi: 10.1056/NEJMoa1905725 [2] NG S C, SHI H Y, HAMIDI N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population based studies[J]. Lancet, 2017, 390(10114): 2769-2778. doi: 10.1016/S0140-6736(17)32448-0 [3] 中华医学会消化病学分会炎症性肠病学组. 炎症性肠病诊断与治疗的共识意见(2018年·北京)[J]. 中国实用内科杂志, 2018, 38(9): 796-813. https://www.cnki.com.cn/Article/CJFDTOTAL-SYNK201809007.htm [4] RUBIN D T, ANANTHAKRISHNAN A N, SIEGEL C A, et al. ACG clinical guideline: Ulcerative Colitis in adults[J]. Am J Gastroenterol, 2019, 114(3): 384-413. doi: 10.14309/ajg.0000000000000152 [5] SANBORN W J, SU C, SANDS B E, et al. Tofacitinib as induction and maintenance therapy for Ulcerative Colitis[J]. N Engl J Med, 2017, 376(18): 1723-1736. doi: 10.1056/NEJMoa1606910 [6] HERMANNS H M, WOHLFAHRT J, MAIS C, et al. Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction[J]. Biol Chem, 2016, 397(8): 695-708. doi: 10.1515/hsz-2015-0277 [7] HARBORD M, ELIAKIM R, BETTENWORTH D, et al. Corrigendum: third european evidence-based consensus on diagnosis and management of Ulcerative Colitis. part 2: Current management[J]. J Crohns Colitis, 2017, 11(12): 1512. doi: 10.1093/ecco-jcc/jjx105 [8] MANGAN M S J, OLHAVA E J, ROUSH W R, et al. Targeting the NLRP3 inflammasome in inflammatory diseases[J]. Nat Rev Drug Discov, 2018, 17(8): 588-606. doi: 10.1038/nrd.2018.97 [9] MOHAMED D A, AHMED S M, KAMAL M M. The role of retinoids in acute renal damage associated with acetic acid induced Ulcerative Colitis in adult male rats: Histological and biochemical study[J]. J Med Syst, 2020, 3(1): 44-58. http://www.researchgate.net/publication/338937343_The_role_of_retinoids_in_acute_renal_damage_associated_with_acetic_acid_induced_ulcerative_colitis_in_adult_male_rats_Histological_and_biochemical_study [10] REN T H, ZHOU Y, WU W Y, et al. Activation of adenosine A3 receptor inhibits NLRP3 inflammasome and pyroptosis of colonic epithelial cells of patients with Ulcerative Colitis[J]. Gastroenterology, 2019, 156(6): s627-637. http://www.researchgate.net/publication/332919040_Su1831_-_Activation_of_Adenosine_A3_Receptor_Inhibits_Nlrp3_Inflammasome_and_Pyroptosis_of_Colonic_Epithelial_Cells_of_Patients_with_Ulcerative_Colitis [11] CLEYNEN I, BOUCHER G, JOSTINS L, et al. Inherited determinants of Crohn's disease and Ulcerative Colitis phenotypes: A genetic association study[J]. Lancet, 2016, 387(10014): 156-167. doi: 10.1016/S0140-6736(15)00465-1 [12] 李芳, 夏菲, 张东波, 等. miR-155在溃疡性结肠炎患者直肠黏膜和外周血单个核细胞中的表达及意义[J]. 中国临床研究, 2017, 30(7): 869-873. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCK201707002.htm [13] 贾立伟, 孙辉, 李欣, 等. 溃疡性结肠炎药物治疗的研究进展[J]. 北京医学, 2018, 40(1): 63-65, 68. https://www.cnki.com.cn/Article/CJFDTOTAL-BJYX201801020.htm [14] 梁笑楠, 尹凤荣, 张晓岚. 炎症性肠病诊断与治疗的共识意见(2018年, 北京)溃疡性结肠炎部分解读[J]. 临床荟萃, 2018, 33(11): 987-990. doi: 10.3969/j.issn.1004-583X.2018.11.016 [15] 中国中西医结合学会消化系统疾病专业委员会. 溃疡性结肠炎中西医结合诊疗共识意见(2017年)[J]. 中国中西医结合消化杂志, 2018, 26(2): 105-111. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXPW201802001.htm -