摘要
目的探讨枯芩、条芩提取物对湿热型溃疡性结肠炎(UC)大鼠肠道菌群的影响及对肠黏膜屏障的保护作用机制。方法50只健康SD大鼠随机分为5组:正常组、模型组、枯芩组、条芩组和美莎拉嗪组,每组10只。采用高脂高糖饲料喂养+高度白酒灌胃+5%葡聚糖硫酸钠(DSS)联合诱导法,建立湿热型UC大鼠模型;各组分别于造模第1天开始灌胃给药,枯芩组、条芩组给药剂量均为5.25 g·kg^(-1)·d^(-1),美沙拉嗪组给药剂量为0.266 g·kg^(-1)·d^(-1),正常组、模型组灌服等体积生理盐水。连续给药28 d。给药结束后,收集大鼠无菌粪便,解剖取大鼠结肠黏膜组织,进行匀浆,Elisa法检测大鼠结肠黏膜白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)炎症因子水平;采用实时荧光定量聚合酶链式反应(qRT-PCR)法检测大鼠结肠组织紧密连接蛋白-1(claudin-1)、黏蛋白2(MUC2)、咬合蛋白(occludin)、闭锁小带蛋白-1(ZO-1)mRNA表达水平;采用16S rDNA测序技术检测大鼠粪便肠道菌群数量及丰度。结果与正常组比较,模型组大鼠结肠黏膜IL-6、TNF-α、IL-1β炎症因子含量均明显上升(P<0.01),Claudin-1、MUC2、Occludin、ZO-1 mRNA表达水平均明显上升(P<0.01);给药28 d后,与模型组比较,各给药组大鼠结肠黏膜IL-6、TNF-α、IL-1β水平均出现显著的降低(P<0.01),Claudin-1、MUC2、Occludin、ZO-1m RNA表达水平均出现不同程度的显著降低(P<0.05或P<0.01);与枯芩组比较,条芩组、美沙拉嗪组在降低IL-6、TNF-α、IL-1β、Claudin-1、Occludin、ZO-1 mRNA表达水平方面均优于枯芩组(P<0.05或P<0.01),对MUC2指标改善不明显,以美沙拉嗪组药效最好。肠道菌群测序结果显示,湿热型UC模型组大鼠肠道菌物种多样性及丰度降低,厚壁杆菌门(firmicutes)、拟杆菌门(bacteroidota)相对丰度明显减少(P<0.05),变形菌门(proteobacteria)相对丰度显著增加(P<0.05),枯芩组、条芩组对厚壁杆菌门、拟�
Objective To investigate the effect of extracts from Pith-decayed and Pith-nodecayed products of Scutellariae Radix on intestinal flora and the protective mechanism of intestinal mucosal barrier in rats with damp-heat ulcerative colitis(UC).Methods Fifty healthy SD rats were randomly divided into 5 groups:normal group,model group,Pith-decayed products of Scutellariae Radix group,Pith-nodecayed products of Scutellariae Radix group and mesalazine group,with 10 rats in each group.The damp-heat UC rat model was established by the combination of high-fat and high-sugar diet+high-liquor administration+5%dextran sodium sulfate(DSS).Each group was given intragastric administration on the first day of modeling,respectively.The dosage of Pith-decayed products group and Pith-nodecayed products group was 5.25 g·kg^(-1)·d^(-1),and that of mesalazine group was 0.266 g·kg^(-1)·d^(-1).Normal group and model group were given equal volume of normal saline.The drug was administered continuously for 28 days.After administration,sterile feces were collected,and the colonic mucous tissues were dissected and homogenized.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in colonic mucosa of rats were detected by Elisa.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of Claudin-1,MUC2,Occludin,ZO-1 in colon tissue of rats.16S rDNA sequencing technology was used to detect the quantity and abundance of intestinal flora in stool of rats.Results Compared with normal group,the contents of IL-6,TNF-αand IL-1βin colonic mucosa of rats in model group were significantly increased(P<0.01),and mRNA expression levels of Claudin-1,MUC2,Occludin and ZO-1 were significantly increased(P<0.01).After 28 days of administration,compared with the model group,the levels of IL-6,TNF-αand IL-1βin colonic mucosa of rats in each administration group were significantly decreased(P<0.01),and the mRNA expression levels of Claudin-1,MUC2,Occludin and
作者
黄伟
罗雅琴
于新阳
董红敬
王晓
HUANG Wei;LUO Yaqin;YU Xinyang;DONG Hongjing;WANG Xiao(Shandong Academy of Chinese Medicine,Institute of Chinese Materia Medica Pharmacology(Pharmacological Experimental Center),Jinan Shandong 250014,China;Qilu University of Technology(Shandong Academy of Sciences),Shandong Analysis and Test Center,Jinan Shandong 250014,China;The Affiliated Hospital of Shandong University of Chinese Medicine(First Clinical College),Jinan Shandong 250014,China)
出处
《中国药物警戒》
2024年第4期408-414,共7页
Chinese Journal of Pharmacovigilance
基金
中央本级重大增减支项目“名贵中药资源可持续利用能力建设项目”(2060302)
国家自然科学基金资助项目(81704029)
山东省自然科学基金联合基金重点资助项目(ZR2022LZY007)
山东省中医药高层次人才培育项目(鲁卫人才字[2023]37号)
齐鲁卫生与健康杰出青年人才资助项目(鲁卫人才字[2020]3号)
山东省中医药科技项目(Z-2022098T、M-2022027)。
关键词
黄芩
枯芩
条芩(或子芩)
提取物
湿热型溃疡性结肠炎
肠道菌群
肠黏膜屏障
大鼠
Scutellariae Radix
Pith-decayed
Pith-nodecayed
extracts
damp-heat ulcerative colitis
intestinal flora
intestinal barrier
rats
