健脾化滞方对脾虚湿热型轻中度溃疡性结肠炎患者肠道菌群及血清炎症因子的影响

Effect of Jianpi Huazhi Recipe on Intestinal Microflora and Serum Inflammatory Factors in Mild-Moderate Ulcerative Colitis Patients with Pi Deficiency and Dampness-Heat Syndrome

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DOI：10.7661/j.cjim.20230410. 043

中文关键词: 健脾化滞方溃疡性结肠炎肠道菌群白细胞介素10 肿瘤坏死因子α Toll 样受体 4 中药

英文关键词:Jianpi Huazhi Recipe ulcerative colitis intestinal flora IL-10 TNF-α TLR4 Chinese herbal medicine

基金项目:南通市卫计委科技项目课题资助（No. WQ2016053）；南通市卫计委青年科研基金项目（No. WKZL2018031）；南通市青年医学人才项目 [No.079（2016年-2020年）]

作者	单位
陈亮,顾庆华,景姗,杨芳,许琰杰,徐逸	南通市中医院南京中医药大学南通附属医院脾胃病科（江苏 226000）

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中文摘要:

目的观察健脾化滞方对脾虚湿热型溃疡性结肠炎（UC）患者治疗前后肠道差异菌属变化，结合血清学指标探讨其作用机制。方法选取门诊2016年8月—2017年6月诊治的36例脾虚湿热型（轻中度慢性复发型）UC患者并另选15名健康者。患者组给予健脾化滞丸10 g，每天3次，连续4周，检测健康者及患者治疗前后白细胞（WBC）、C-反应蛋白（CRP）、血沉（ESR）的水平，比较各组血清中肿瘤坏死因子α（TNF-α）、白细胞介素10（IL-10）、IL-12、IL-23、Toll样受体4（TLR4）的表达水平，运用16S rDNA测序与技术分析健康者群及脾虚湿热型UC患者治疗前后肠道粪便菌群变化。结果与治疗前比较，患者治疗后ESR、TNF-α、IL-12、IL-23降低（P<0.01，P<0.05），IL-10表达升高（P<0.05），其他指标表达比较差异无统计学意义（P>0.05）。与治疗前比较，患者治疗后肠道菌群OTU数量明显增多，在科水平上巴斯德氏菌科、肠杆菌科相对表达含量下降，普雷沃氏菌科、氨基酸球菌科比例上升。在属水平上巨球形菌属、副沙门氏菌属、厌氧菌属、毛螺菌属丰度下降，巨细胞菌属、氨基酸球菌属比例上升。在种水平上脆弱拟杆菌、大肠杆菌志贺菌属下g_Escherichia-Shigella_Unclassified、厌氧菌属下的g_Anaerostipes_Unclassified比例下降，巨单胞菌属下g_Megamonas_Unclassified、氨基酸球菌属下的g_Acidaminococcus_Unclassified比例上升，且治疗后菌群组成结构、丰度趋近于健康组。结论健脾化滞方对脾虚湿热型UC患者具有调节肠道菌群结构，增加拟杆菌丰度，减少致病菌繁殖作用，并调节患者血清中炎症因子的表达，改善局部免疫平衡。

英文摘要:

Objective To observe the changes of intestinal flora in ulcerative colitis（UC）patients with Pi deficiency and dampness-heat syndrome（PDDHS）treated with Jianpi Huazhi Recipe（JPHZR）before and after treatment， and to explore its mechanism combined with serological indexes. Methods Totally 36 UC outpatients with PDDHS（mild-moderate， chronic recurrence）from August 2016 to June 2017 and healthy participants（15 cases）were selected. The patient group was given 10 g Jianpi Huazhi Pill 3 times a day for 4 weeks. The levels of white blood cell（WBC）， C-reactive protein（CRP）and erythrocyte sedimentation rate（ESR）were detected in healthy participants and patients before and after treatment. The expression levels of tumor necrosis factorα（TNF-α）， interleukin-10（IL-10）， IL-12， IL-23， and Toll like receptor 4（TLR4）were compared in each group. The changes of intestinal fecal flora in healthy participants and UC patients with PDDHS before and after treatment were analyzed using 16S rDNA sequencing and technology. Results Compared with those before treatment， ESR，TNF-α， IL-12， and IL-23 decreased after treatment （P<0.01， P<0.05）， IL-10 expression increased（P<0.05）， there was no significant difference in other indicators（P>0.05）.Compared with that before treatment， the number of intestinal flora OTU in patients increased significantly after treatment. At the family level， the relative expression content of Pasteurellaceae and Enterobacteriaceae decreased， and the proportion of Prevotellaceae，and Acidaminococcaceae increased. At the genus level， the abundance of Megasphaera， Parasalmonella， Anaerostipes，and Lachnospira decreased， while the proportion of Megamonas and Acidaminococcus increased. At species level， the proportion of Bacteroides fragilis， Escherichia coli and Shigellag_Escherichia-Shigella_Unclassified， Anaerostipesg_Anaerostipes_Unclassified decreased， and g_Megamonas_Unclassified belongs to Macromonasspp， g_Acidaminococcus_Unclassified of amino acid cocci increased， and the composition， structure and abundance of flora after treatment tended to be similar to the healthy group. Conclusion JPHZR could regulate the intestinal flora structure， increase the abundance of Bacteroides， reduce the reproduction of pathogenic bacteria， significantly regulate the expression of inflammatory factors in patients' serum， and improve the local immune balance in UC patients with PDDHS.

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