黄连解毒汤对湿热下注型肛瘘患者肠道菌群的影响  

Effect of Huanglian Jiedu Decoction on intestinal flora in patients of anal fistula with dampness-heat diffused downward type

作　　者：朱静怡 张玲[1] 柳奕诚 张俊 黄进 毛畅 梅祖兵[1] 胡峻[2] 汪庆明[1] ZHU Jingyi;ZHANG Ling;LIU Yicheng;ZHANG Jun;HUANG Jin;MAO Chang;MEI Zubing;HU Jun;WANG Qingming(Department of Anorectal Surgery,Shuguang Hospital Affiliated to Shanghai Univrrsity of Traditional Chinese Medicine,Shanghai 201203,China;Department of General Surgery,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肛肠科,上海201203 [2]上海中医药大学附属曙光医院普外科,上海201203

出　　处：《上海中医药大学学报》2022年第4期12-18,25,共8页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81774112);上海市科委医学引导类(中、西医)科技支撑项目(19401933900)。

摘　　要：目的:采用16S rDNA高通量测序,观察黄连解毒汤对湿热下注型肛瘘患者肠道菌群的影响。方法:纳入湿热下注型肛瘘患者40例,随机分为中药组和对照组,每组各20例。两组患者均予括约肌间瘘管结扎术(LIFT)治疗,中药组患者在术前予黄连解毒汤口服2周。于术前1 d采集血清和粪便标本,采用酶联免疫吸附法(ELISA)检测两组患者的血清白介素(IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ和IFN-α水平,采用16S rDNA高通量测序检测两组患者粪便的肠道菌群组成;于术后第12周评估临床疗效。结果:中药组患者的IL-8、IFN-γ、IFN-α水平低于对照组(P<0.05),且中药组的临床疗效显著优于对照组(P<0.05)。16S rDNA高通量测序和生化分析结果显示,两组肠道微生物群存在显著差异。在门(Phylum)水平上,放线杆菌门(Actinobacteriota)、蓝藻门(Cyanobacteria)主要富集于中药组(P<0.05),而梭杆菌门(Fusobacteriota)主要富集于对照组(P<0.05)。功能富集分析结果显示,细菌类核DNA结合蛋白、铁肠螯蛋白和大肠杆菌素的外膜受体等在中药组中富集(P<0.05)。通路预测结果显示,肽聚糖生物合成和细胞色素c等代谢通路在对照组中富集(P<0.05)。结论:黄连解毒汤的抗菌抗炎作用可能是通过改善肛瘘患者肠道菌群,降低有害细菌的相对丰度,升高有益细菌的相对丰度,并可能与增加细菌类核DNA结合蛋白的表达,增加铁肠螯蛋白和大肠杆菌素的外膜受体的表达,抑制肽聚糖合成和细胞色素c等代谢通路有关。因此,该方可作为肛瘘患者的术前辅助治疗方式,或作为保守治疗及无法及时入院手术治疗的备选方案。Objective:To observe the effect of Huanglian Jiedu Decoction on intestinal flora in patients of anal fistula with dampness-heat diffused downward type by the technique of 16S rDNA high-throughput sequencing.Methods:A total of 40 patients of anal fistula with dampness-heat diffused downward type were included and randomly divided into the traditional Chinese medicine group and control group,20 cases in each group. The patients in both groups were treated with ligation of intersphincteric fistula tract(LIFT),and the patients in the traditional Chinese medicine group were orally treated with Huanglian Jiedu Decoction before operation for 2 weeks. One day before operation,the serum and fecal samples were collected. The levels of serum interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,tumor necrosis factor-α(TNF-α),interferon(IFN)-γ and IFN-α were detected by ELISA. The composition characteristics of fecal intestinal flora in both groups were detected by 16S rDNA high-throughput sequencing. Twelve weeks after operation,the clinical effect was evaluated.Results:The levels of IL-8,IFN-γ and IFN-α in the traditional Chinese medicine group were lower than those in the control group(P<0.05),and the clinical efficacy of the traditional Chinese medicine group was significantly better than that of the control group(P<0.05). The results of 16S rDNA high-throughput sequencing and biochemical analysis showed that there were significant differences in the intestinal microbiota between the two groups. On the level of Phylum,the Actinobacteriota and Cyanobacteria Phylums were mainly enriched in the traditional Chinese medicine group(P<0.05),while the Fusobacteriota Phylum was mainly enriched in the control group(P<0.05). The results of functional enrichment analysis showed that the bacterial nucleoid DNA-binding protein and outer membrane receptor for ferrienterochelin and colicins were enriched in the traditional Chinese medicine group(P<0.05). The results of pathway prediction showed that the metabolic pathw

关 键 词：肛瘘 湿热下注型 肠道菌群 黄连解毒汤 16S rDNA 

分 类 号：R266[医药卫生—中医外科学]