清肠化瘀方治疗溃疡性结肠炎疗效及对IDO、Treg/Th17平衡的影响

Clinical Efficacy of Qingchang Huayu Prescription in the Treatment of Ulcerative Colitis and Its Effect on IDO and Treg/Th17 Balance

【目的】观察清肠化瘀方治疗溃疡性结肠炎(ulcerative colitis,UC)的临床疗效,并探讨其治疗机制。【方法】将96例大肠湿热型活动期UC患者随机分为研究组和对照组,每组各48例。2组患者均给予美沙拉嗪肠溶片口服,研究组同时给予口服中药清肠化瘀方治疗,对照组同时给予口服清肠化瘀方低剂量配方颗粒(安慰剂,药物含量为试验药品的2.5%)治疗,2组疗程均为12周。观察2组患者治疗前后中医证候评分、改良Mayo评分、Baron内镜评分、血清吲哚胺2,3双加氧酶(IDO)、白细胞介素(IL)-10、转化生长因子β(TGF-β)、IL-17、IL-21水平和外周血调节性T淋巴细胞(Treg)、辅助性T细胞17(Th17)含量的变化情况,并比较2组患者的临床疗效(包括有效率和缓解率)及肠镜疗效(包括内镜应答率和黏膜愈合率)。【结果】(1)治疗12周后,研究组的临床有效率、临床缓解率、内镜应答率、黏膜愈合率分别为95.83%(46/48)、83.33%(40/48)、97.92%(47/48)、91.67%(44/48),对照组分别为75.00%(36/48)、60.42%(29/48)、79.17%(38/48)、70.83%(33/48),组间比较,研究组的临床有效率、临床缓解率、内镜应答率、黏膜愈合率均高于对照组(P<0.05或P<0.01)。(2)治疗后,2组患者的腹痛、腹泻、脓血便、里急后重等各项中医证候评分以及改良Mayo评分和Baron内镜评分均较治疗前明显降低(P<0.01),且研究组的降低作用均明显优于对照组(P<0.01)。(3)治疗后,2组患者的血清IDO、IL-17、IL-21水平和外周血Th17含量均较治疗前明显降低(P<0.01),血清IL-10、TGF-β水平和外周血Treg含量均较治疗前明显升高(P<0.01),且研究组对血清IDO、IL-17、IL-21水平和外周血Th17含量的降低作用以及对血清IL-10、TGF-β水平和外周血Treg含量的升高作用均明显优于对照组(P<0.01)。【结论】清肠化瘀方应用于大肠湿热型活动期UC的治疗,可有效改善患者中医证候,促进肠黏膜的修复和愈合,临床疗效和肠镜疗效更优,其机制可能与通过抑制IDO的高表达而调节Treg/Th17平衡有关。

Objective To observe the clinical efficacy of Qingchang Huayu Prescription in the treatment of ulcerative colitis(UC)and to preliminarily explore its therapeutic mechanism.Methods Ninety-six patients with active UC of large intestine damp-heat syndrome type were randomly divided into the study group and the control group,with 48 patients in each group.Both groups of patients were given oral use of Mesalazine Enteric-coated Tablets,and additionally,the study group was given oral administration with Qingchang Huayu Prescription,and the control group was given oral administration with placebo of low-dose granules of Qingchang Huayu Prescription(2.5%drug content of the test medicine).Both groups of patients were treated for 12 weeks.The changes in traditional Chinese medicine(TCM)syndrome score,modified Mayo score,Baron endoscopic score,serum indoleamine 2,3 dioxygenase(IDO),interleukin(IL)-10,transforming growth factorβ(TGF-β),IL-17 and IL-21 levels,and peripheral regulatory T lymphocyte(Treg)and helper T cell 17(Th17)levels in the two groups were observed before and after treatment.After treatment,the clinical efficacy(including effective rate and remission rate)and the colonoscopic efficacy(including endoscopic response rate and mucosal healing rate)were compared in the two groups.Results(1)After 12 weeks of treatment,the clinical effective rate,clinical remission rate,endoscopic response rate and mucosal healing rate of the study group were 95.83%(46/48),83.33%(40/48),97.92%(47/48)and 91.67%(44/48)respectively,and were 75.00%(36/48),60.42%(29/48),79.17%(38/48)and 70.83%(33/48)in the control group respectively.The intergroup comparison showed that the clinical effective rate,clinical remission rate,endoscopic response rate and mucosal healing rate of the study group were all higher than those of the control group(P<0.05 or P<0.01).(2)After treatment,the scores of all the TCM symptoms such as abdominal pain,diarrhea,purulent and bloody stool,and tenesmus as well as the modified Mayo score and Baron endoscopic score in the two groups were significantly lower than those before treatment(P<0.01),and the effect on lowering those scores in the study group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum IDO,IL-17,and IL-21 levels and peripheral Th17 level in both groups were significantly decreased compared with those before treatment(P<0.01),and the serum IL-10 and TGF-βlevels and peripheral Treg level were significantly increased compared with those before treatment(P<0.01).The effect on lowering serum IDO,IL-17,and IL-21 levels and peripheral TH17,and the effect on increasing serum IL-10 and TGF-βlevels and peripheral Treg level of the study group were all significantly superior to that of the control group(P<0.01).Conclusion The application of Qingchang Huayu Prescription in the treatment of UC with large intestine damp-heat syndrome type is effective on improving the TCM syndrome and promoting the repair and healing of intestinal mucosa with superior clinical efficacy and colonoscopic efficacy.The mechanism may be related to the regulation of Treg/Th17 balance by inhibiting the increased expression of IDO.