【目的】 探讨青赤散（由炉甘石、赤石脂、黄柏、苦参、儿茶、青黛、白及、三七粉组成）保留灌肠对溃疡性结肠炎 （UC）患儿肠道菌群及外周血单个核细胞Toll样受体4（TLR4）/NOD样受体热蛋白结构域相关蛋白3（NLRP3）信号通路的影响。 【方法】 将 2022年 1月至 2024年 3月衡水市人民医院收治的 100例 UC患儿随机分为对照组与研究组，每组各 50例。对照组 给予美沙拉嗪肠溶片口服治疗，研究组在对照组的基础上加用青赤散保留灌肠，连续治疗8周。观察2组患儿治疗前后肠道 菌群及外周血单个核细胞内TLR4、NLRP3 mRNA相对表达量和血清TLR4、NLRP3蛋白水平以及血清炎症因子肿瘤坏死因子 α（TNF-α）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）水平的变化情况，评价2组患儿的临床疗效，并采用Spearman检验 分析 UC 患儿外周血单个核细胞 TLR4、NLRP3 mRNA 相对表达量及血清 TLR4、NLRP3蛋白含量与疗效总有效率的相关性。 【结果】（1）临床疗效方面，治疗8周后，研究组的总有效率为94.00%（47/50），对照组为70.00%（35/50），组间比较（χ2 检验）， 研究组的疗效明显优于对照组（P＜0.01）。（2）肠道菌群方面，治疗后，2组患儿的肠球菌和肠杆菌数量较治疗前显著减少（P＜ 0.05），双歧杆菌和乳酸杆菌数量较治疗前明显增多（P＜0.05）；治疗后组间比较，研究组的肠球菌和肠杆菌数量均明显少于 对照组（P＜0.05），双歧杆菌和乳酸杆菌数量均明显多于对照组（P＜0.05）。（3）外周血单个核细胞 TLR4、NLRP3 mRNA相对 表达量方面，治疗后，2组患儿的外周血单个核细胞TLR4、NLRP3 mRNA相对表达量均较治疗前明显降低（P＜0.05），且研 究组的外周血单个核细胞TLR4、NLRP3 mRNA相对表达量均明显低于对照组（P＜0.05）。（4）血清TLR4、NLRP3蛋白水平方 面，治疗后，2组患儿的血清TLR4、NLRP3蛋白水平均较治疗前明显降低（P＜0.05），且研究组的血清TLR4、NLRP3蛋白水 平均明显低于对照组（P＜0.05）。（5）血清炎症因子水平方面，治疗后，2组患儿的血清TNF-α、IL-1β、IL-6水平均较治疗前 明显降低（P＜0.05），且研究组的血清TNF-α、IL-1β、IL-6水平均明显低于对照组，差异均有统计学意义（P＜0.05）。（6）相 关性分析方面，经Spearman检验，UC患儿外周血单个核细胞TLR4、NLRP3 mRNA相对表达量及血清TLR4、NLRP3蛋白水 平与疗效总有效率均呈显著负相关（P＜0.001）。【结论】 青赤散保留灌肠可以下调 UC患儿外周血单个核细胞 TLR4/NLRP3通 路关键分子表达，调节患儿肠道菌群，改善机体炎性状态，具有显著疗效。

Objective To investigate the effect of Qingchi Powder （composed of calamina，Halloysitum Rubrum， Phellodendri Chinensis Cortex， Sophorae Flavescentis Radix， Catechu， Indigo Naturalis， Rhizoma Bletillae， and Notoginseng Radix et Rhizoma powder） retention enema on intestinal flora and Toll-like receptor 4（TLR4）/ NOD-like receptor thermoprotein domain-related protein 3（NLRP3） signaling pathway in peripheral blood mononuclear cell （PBMC） of children with ulcerative colitis （UC）. Methods A total of 100 children with UC were randomly divided into control group and study group，with 50 cases in each group. The control group was treated with oral administration of Mesalazin Enteric-Coated Tablets， and the study group was treated with Qingchi Powder retention enema on the basis of treatment for the control group. The treatment for the two groups lasted for 8 consecutive weeks. Before and after treatment，the distribution of intestinal flora and the relative mRNA expression levels of TLR4 and NLRP3 in PBMC， serum contents of TLR4 and NLRP3 protein， and serum levels of inflammatory factors such as tumor necrosis factor α（TNF-α），interleukin 1β（IL-1β） and interleukin 6（IL-6） in the two groups were observed. After treatment， the clinical efficacy of the two groups was evaluated， and Spearman test was used to analyze the correlation of total effective rate with the relative mRNA expression levels of TLR4 and NLRP3 in PBMC and serum contents of TLR4 and NLRP3 protein. Results （1） After 8 weeks of treatment， the total effective rate of the study group was 94.00%（47/50）， and that of the control group was 70.00% （35/50）. The intergroup comparison （tested by chi-square test） showed that the efficacy of the study group was significantly superior to that of the control group（P＜0.01）.（2）After treatment，the number of Enterococcus and Enterobacteriaceae in the two groups was significantly lowered （P＜0.05），and the number of Bifidobacterium and Lactobacillus was significantly increased compared with that before treatment （P＜0.05）. After treatment，the number of Enterococcus and Enterobacteriaceae in the study group was significantly lower （P＜0.05） and the number of Bifidobacterium and Lactobacillus was significantly higher than that in the control group （P＜0.05）. （3）After treatment，the mRNA relative expression levels of TLR4 and NLRP3 in PBMC of the two groups were significantly decreased compared with those before treatment（P＜0.05），and the levels in the study group were significantly lower than those in the control group（P＜0.05）.（4）After treatment，the serum TLR4 and NLRP3 protein levels in the two groups were significantly decreased compared with those before treatment （P＜0.05），and the levels in the study group were significantly lower than those in the control group （P＜0.05）.（5） After treatment，the levels of serum inflammatory factors of TNF- α，IL-1β and IL-6 in the two groups significantly decreased compared with those before treatment （P＜0.05），and the levels in the study group were significantly lower than those in the control group （P＜0.05）.（6） Spearman correlation analysis showed that the mRNA relative expression levels of TLR4 and NLRP3 in PBMC and serum TLR4 and NLRP3 protein levels in children with UC were significantly negatively correlated with the total effective rate of curative effect （P＜0.001）. Conclusion Qingchi Powder retention enema can down-regulate the expression levles of key signaling molecules of TLR4/ NLRP3 pathway in PBMC of children with UC， regulate the intestinal flora of children， and improve the inflammatory response. It has significant curative effect and is worthy of expanding its application in clinic.

R259.746

国家自然科学基金资助项目（编号：82374351）