基于16S rDNA测序探讨滋肾通关方对慢性非细菌性前列腺炎大鼠“肠-前列腺”轴的影响  

Effect of Zishen Tongguan Formula on"Gut-prostate"Axis of Rats with Chronic Non-bacterial Prostatitis Based on 16S rDNA Sequencing

作　　者：李晰然 陈梦娇 邹恺平 赵晨光 代兴斌 张晓清 刘顺 LI Xiran;CHEN Mengjiao;ZOU Kaiping;ZHAO Chenguang;DAI Xingbin;ZHANG Xiaoqing;LIU Shun(Jiangsu Engineering Research Centre for Innovative Chinese Medicine Preparations,Jiangsu Integration Innovation Centre for Specialty Chinese Medicine Preparations,Affiliated Hospital of Nanjing University of Chinese Medicine/Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China;The First Clinical College of Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学附属医院/江苏省中医院,江苏省中医创新制剂工程研究中心,江苏省中药特色制剂融合创新中心,南京210029 [2]南京中医药大学第一临床医学院,南京210023

出　　处：《中国实验方剂学杂志》2025年第7期63-71,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81603310);江苏省自然科学基金面上项目(BK20211395);江苏省中医药科技发展计划重点项目(ZD202006);江苏省中医药科技发展计划面上项目(MS2022019,MS2022022);江苏省中医疫病研究中心开放课题(JSYB2024KF11);南京市医疗机构中药传统制剂研究项目(NJCC-ZJ-202344)。

摘　　要：目的:基于“肠-前列腺”轴理论,通过检测炎症因子表达水平和慢性非细菌性前列腺炎(CNP)大鼠肠道菌群的组成结构,探究滋肾通关方及方中肉桂治疗CNP大鼠的作用与机制。方法:42只SD大鼠随机挑选8只作为正常组,其余动物采用注射角叉菜胶的方法制备CNP模型,造模成功后将其中32大鼠随机分为模型组、宁泌泰胶囊组(0.50 g·kg^(-1))、滋肾通关方组(2.00 g·kg^(-1))、黄柏-知母药对组(2.00 g·kg^(-1)),每组8只,给药组分别给予相应药液灌胃,正常组和模型组给予等量生理盐水灌胃,1次/d,连续给药14 d。收集大鼠前列腺组织并进行苏木素-伊红(HE)染色和马松(Masson)染色,观察各组大鼠前列腺组织病理变化。利用酶联免疫吸附测定法(ELISA)检测大鼠血清中白细胞介素-8(IL-8)、超敏C-反应蛋白(hs-CRP)、免疫球蛋白M(IgM)、分泌型IgA(sIgA)、诱导型一氧化氮合酶(iNOS)、转化生长因子-β(1 TGF-β_(1))水平。利用16S rDNA测序分析给药前后肠道菌群变化。结果:各给药组均可缓解CNP大鼠的炎症症状,提高抗炎因子的表达水平,降低促炎因子的表达水平,以滋肾通关方组最明显。与正常组比较,模型组大鼠IL-8、hs-CRP、sIgA、IgM、iNOS表达水平均显著增加(P<0.01);与模型组比较,各个给药组上述炎症因子表达水平均显著降低(P<0.01);与黄柏-知母药对组比较,滋肾通关方组TGF-β_(1)表达水平明显降低(P<0.05),IgM表达水平显著增加(P<0.01)。肠道菌群结果显示,与黄柏-知母药对组比较,在目水平上,滋肾通关方组可以显著降低条件致病菌拟杆菌目(Bacteroidales)、Acidaminococcales、红螺菌目(Rhodospirillales)、梭菌目(Clostridiales)、迷踪菌目(Elusimicrobiales)菌群的相对丰度(P<0.01);在属水平上,显著降低致病菌毛螺菌属和拟杆菌属菌群的相对丰度(P<0.01),显著增加有益菌瘤胃球菌属和乳酸杆菌属等菌群的相对丰度(P<0.01)。结论:滋肾通关�Objective:Based on the theory of"gut-prostate"axis,this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis(CNP)by detecting the levels of inflammatory factors,and the composition and structure of intestinal flora in CNP rats.Methods:Eight out of 42 SD rats were randomly selected as the normal group,and the remaining rats were injected with carrageenan to prepare the CNP model.After successful modeling,32 rats were randomly divided into the model group,Ningmitai capsule group(0.50 g·kg^(-1)),Zishen Tongguan formula group(2.00 g·kg^(-1)),and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group(PCC-AR group,2.00 g·kg^(-1)),with 8 rats in each group.The administered groups were given the corresponding medicinal solution by gavage,and the normal and model groups were intragastrically administered with an equal volume of normal saline,once a day for 14 consecutive days.The prostate tissues of rats were collected and subjected to hematoxylin-eosin(HE)staining and Masson staining to observe the pathological changes of the tissues in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of related inflammatory factors in rat serum,and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration,and species difference analysis was performed.Results:All the administered groups could alleviate the inflammatory symptoms of CNP rats,increase the expression levels of antiinflammatory factors and decrease the expression levels of pro-inflammatory factors,with the most sIgnificant effect observed in the Zishen Tongguan formula group.Compared with the normal group,the expression levels of interleukin(IL)-8,hypersensitive C-reactive protein(hs-CRP),immunoglobulin(Ig)M,secretory IgA(sIgA),and inducible nitric oxide synthase(iNOS)were sIgnificantly increased in the model group(P<0.01).Compared with the model group,the e

关 键 词：慢性非细菌性前列腺炎 肠道菌群 炎症因子 滋肾通关方 “肠-前列腺”轴 16S rDNA测序 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R697[生物学—微生物学] Q939.121