Effects of Gegen Hongteng Jiedu Decoction on serum NLRP3 inflammasome, IL-18, IL-1β, intestinal flora and mucosal barrier in patients with turbidium-toxic ulcerative colitis
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摘要: 目的 观察葛根红藤解毒汤对溃疡性结肠炎患者的血清核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomeric dome-like receptor protein 3，NLRP3)炎症小体、IL-1β、IL-18表达水平与对肠道菌群、黏膜屏障的影响。方法 将90例浊毒内蕴型溃疡性结肠炎患者随机分为观察组和对照组，每组各45例。对照组予美沙拉嗪肠溶片治疗，观察组在对照组基础上加葛根红藤解毒汤治疗，疗程均为8周。比较两组治疗前后的中医证候积分、血清NLRP3炎症小体、IL-1β、IL-18、二胺氧化酶(diamine oxidase, DAO)、D-乳酸的变化情况及肠道菌群数量。结果 治疗8周后，观察组的总有效率为91.11%(41/45)，对照组为73.33%(33/45)，观察组的疗效明显优于对照组(P＜0.05)。治疗后，两组患者的中医证候积分均较治疗前降低(P＜0.05)，观察组的中医证候积分均明显低于对照组(P＜0.05)。治疗后，两组患者的血清NLRP3炎症小体、IL-1β、IL-18、DAO、D-乳酸水平均较治疗前降低(P＜0.05)，且观察组的血清NLRP3炎症小体、IL-1β、IL-18、DAO、D-乳酸水平明显低于对照组(P＜0.05)。两组治疗前后肠道菌群数量比较均差异有统计学意义(P＜0.05)。治疗期间两组患者的不良反应有腹部胀满、恶心、消化不良，对照组发生率为11.11%，观察组发生率为8.89%，两组间发生率比较差异无统计学意义(P>0.05)。结论 对于浊毒内蕴型溃疡性结肠炎患者，单用美沙拉嗪肠溶片治疗效果欠佳，与葛根红藤解毒汤联合治疗效果显著，不仅能抑制血清炎症因子水平、缓解肠道炎症，还能保护肠黏膜屏障、调节患者肠道菌群，提高临床疗效。Abstract: Objective To observe the effects of Gegen Hongteng Jiedu Decoction on the expression levels of serum nucleotide-binding oligomeric dome-like receptor protein 3(NLRP3) inflammatome, interleukin-1β(IL-1β), interleukin-18(IL-18) and intestinal flora and mucosal barrier in patients with ulcerative colitis.Methods Ninety patients with ulcerative colitis were randomly divided into the observation group and the control group, 45 cases in each group. The control group was treated with mesalazine enteric-coated tablets, and the observation group was treated with Gegen Hongteng Jiedu Decoction on the basis of the control group. The course of treatment was 8 weeks. Traditional Chinese Medicine(TCM) syndrome score, serum NLRP3 inflammasome, IL-1β, IL-18, diamine oxidase(DAO), D-lactic acid and intestinal flora were compared between the two groups before and after treatment.Results After 8 weeks of treatment, the total effective rate of the observation group was 91.11%(41/45) and that of the control group was 73.33%(33/45). The efficacy of the observation group was significantly higher than that of the control group(P < 0.05). The scores of TCM symptoms in both groups were lower than before treatment(P < 0.05), and the scores of TCM symptoms in the observation group after treatment were significantly lower than those in the control group(P < 0.05). Serum levels of NLRP3 inflammasome, IL-1β, IL-18, DAO and D-lactic acid in 2 groups were lower than before treatment(P < 0.05), and serum levels of NLRP3 inflammasome, IL-1β, IL-18, DAO and D-lactic acid in observation group after treatment were significantly lower than those in the control group(P < 0.05). Before and after treatment, there was a statistically significant difference in the number of postintestinal flora(P < 0.05). During treatment, the adverse reactions of the two groups included abdominal distension, nausea and dyspepsia, the incidence of which was 11.11% in the control group and 8.89% in the observation group, with no statistical difference between the two groups(P>0.05).Conclusion For patients with ulcerative colitis with turbidity toxin, mesalazine enteric-coated tablets alone have poor therapeutic effect, while the combined treatment with Gegen Hongteng Jiedu Decoction has significant therapeutic effect, which can not only inhibit serum inflammation level, relieve intestinal inflammation, but also protect intestinal mucosal barrier, regulate intestinal flora of patients, and improve clinical efficacy.
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表 1 两组患者的临床疗效比较
例(%) 组别 例数 痊愈 显效 有效 无效 总有效 观察组 45 12(26.67) 19(42.22) 10(22.22) 4(8.89) 41(91.11)1) 对照组 45 6(13.33) 12(26.67) 15(33.33) 12(26.67) 33(73.33) 与对照组比较，1)P＜0.05。 
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表 2 两组患者治疗前后中医证候积分的比较
分，X±S 组别 例数 便溏腹泻 脘腹疼痛 黏液脓血便 脘腹胀满 里急后重 口干口苦 肛门灼热 观察组 45 治疗前 5.35±2.37 4.75±2.25 4.65±2.53 1.92±0.68 1.79±0.93 1.72±0.84 1.65±0.90 治疗后 2.05±1.951)2) 1.93±1.721)2) 1.64±1.821)2) 0.83±0.751)2) 0.98±0.721)2) 0.69±0.731)2) 0.62±0.591)2) 对照组 45 治疗前 5.56±2.48 4.89±2.51 4.57±2.39 2.13±0.75 1.83±0.86 1.63±0.89 1.60±0.98 治疗后 3.95±2.591) 2.75±1.921) 3.28±2.251) 1.94±0.821) 1.45±0.741) 1.32±0.831) 0.94±0.871) 与本组治疗前比较，1)P＜0.05；与对照组比较，2)P＜0.05。
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表 3 两组患者治疗前后血清NLRP3炎症小体、IL-1β、IL-18水平的比较
pg/mL，X±S 组别 例数 NLRP3炎症小体 IL-1β IL-18 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 45 696.20±72.24 395.70±28.671)2) 72.93±5.30 32.06±8.311)2) 89.64±9.39 38.31±14.431)2) 对照组 45 687.90±57.61 476.30±62.371) 70.33±4.05 40.75±5.951) 92.13±12.31 56.96±8.281) 与本组治疗前比较，1)P＜0.05；与对照组比较，2)P＜0.05。
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表 4 两组患者治疗前后肠道菌群数量的比较
IgCFU/g，X±S 组别 例数 肠球菌 肠杆菌 乳酸杆菌 双歧杆菌 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 45 8.75±0.83 5.38±0.731)2) 9.85±0.93 8.01±0.651)2) 5.95±0.91 9.57±0.851)2) 5.37±0.71 9.73±0.671)2) 对照组 45 9.14±0.79 7.32±0.741) 10.14±0.98 9.75±0.891) 5.67±0.79 7.32±0.741) 5.25±0.82 7.01±0.761) 与本组治疗前比较，1)P＜0.05；与对照组比较，2)P＜0.05。
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表 5 两组患者治疗前后肠屏障功能的比较
X±S 组别 例数 DAO/(ng/L) D-LA/(mg/L) 治疗前 治疗后 治疗前 治疗后 观察组 45 18.21±2.87 8.45±1.561)2) 14.78±3.22 6.29±1.471)2) 对照组 45 17.91±3.23 11.39±1.841) 15.09±3.78 10.23±2.991) 与本组治疗前比较，1)P＜0.05；与对照组比较，2)P＜0.05。
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表 6 两组患者治疗期间的不良反应情况
例(%) 组别 例数 腹部胀满 恶心 呕吐 消化不良 总发生 观察组 45 2(4.44) 1(2.22) 0 1(2.22) 4(8.89) 对照组 45 3(6.66) 2(4.44) 0 0 5(11.11)
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