小承气汤对重型颅脑损伤模型大鼠急性期肠道菌群的影响  

Effects of Xiaochengqi Decoction(小承气汤)on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury

作　　者：彭玲玲 梁仁久 宁玲 杜宜衡 黄贵华[1] PENG Lingling;LIANG Renjiu;NING Ling;DU Yiheng;HUANG Guihua(Guangxi University of Chinese Medicine,Nanning 530020;The First Affiliated Hospital of Guangxi Medical University;Hunan University of Chinese Medicine)

机构地区：[1]广西中医药大学,广西壮族自治区南宁市530200 [2]广西医科大学第一附属医院 [3]湖南中医药大学

出　　处：《中医杂志》2022年第12期1170-1178,共9页Journal of Traditional Chinese Medicine

基　　金：广西壮族自治区卫生厅中医药科技专项(GZLC14-29);广西名中医传承工作室项目(2017-2);广西中医药大学博士研究生科研创新项目(bs004)。

摘　　要：目的从肠道菌群角度探讨小承气汤治疗重型颅脑损伤(sTBI)的可能作用机制。方法将90只SD大鼠随机分为正常组、假手术组、模型组、金双歧组、小承气汤组,每组18只。模型组、金双歧组、小承气汤组大鼠采用Freeney’s自由落体法制作sTBI大鼠模型,造模成功6 h后,金双歧组、小承气汤组分别给予金双歧6.17 g/kg和小承气汤2.78 g/kg灌胃干预,正常组、假手术组、模型组给予2.78 ml/(kg·d)生理盐水灌胃。干预7 d后观察大鼠神经功能缺损(NSS)评分,HE染色观察脑、结肠组织病理改变,16S rRNA测序技术分析大鼠结肠菌群的变化,蛋白质免疫印迹法检测大鼠脑、结肠组织白细胞介素1β(IL-1β)表达,酶联免疫吸附试验检测血清IL-1β含量。结果假手术组与正常组各指标差异均无统计学意义(P>0.05)。与正常组比较,模型组大鼠体重下降、NSS评分升高(P<0.01)。HE染色显示,模型组大鼠神经细胞排列紊乱,大量神经元坏死,散在存活的神经细胞肿胀、间质疏松,结肠黏膜完整性破坏、肠腺排列紊乱、肠间隙增宽、黏膜水肿,脑、结肠组织和血清IL-1β水平升高(P<0.01),模型组大鼠肠道菌群多样性香农(Shannon)和辛普森(Simpson)指数下降,厚壁菌门、螺旋体门相对丰度下降,拟杆菌门、变形菌门、迷踪菌门、放线菌门、广古菌门相对丰度升高,毛螺科、瘤胃菌科、拟杆菌科_S24-7_组、螺旋体科相对丰度明显下降,拟杆菌科、迷踪菌科、肠杆菌科、产碱杆菌科相对丰度上升,毛螺科_NK4A136_组、毛螺科_UCG-005、罗姆布茨菌属、罗氏菌属、普雷沃氏菌_NK3B31_组、普雷沃氏菌_UCG-001、异普雷沃氏菌属、螺旋体_2相对丰度明显下降,拟杆菌属、埃希志贺菌、副拟杆菌属、迷踪门菌属相对丰度上升(P<0.05或P<0.01)。与模型组比较,小承气汤组和金双歧组大鼠体重升高、NSS评分下降(P<0.05或P<0.01),脑和结肠组织病理改变减轻,Objective To explore the possible mechanism of Xiaochengqi Decoction(小承气汤,XCQD)in the treatment of rats with acute severe traumatic brain injury(sTBI)from the perspective of intestinal flora.Methods A total of 90 SD rats were randomly divided into normal group,sham operation group,model group,golden bifid group and XCQD group,with 18 rats in each group.The sTBI rat model was made using Freeney’s free fall method in the model group,golden bifid group and XCQD group.Six hours after successful modeling,6.17 g/kg of golden bifid and 2.78 g/kg of XCQD was given into the corresponding group by gavage,respectively,while 2.78 ml/(kg·d)of normal saline were administered by gavage in the normal group,sham operation group and model group.After seven days of intervention,the neurological severity score(NSS)was assessed.Pathological changes of brain tissue and colon were observed through hematoxylin eosin(HE)staining,and changes of colon flora were analyzed by 16S rRNA sequencing.The expression of interleukin-1beta(IL-1β)in brain and colon tissue was detected by Western blotting,and serum IL-1βlevel was detected by enzyme-linked immunosorbent assay(ELISA).ResultsThere was no significant difference between the normal and sham operation group in all outcomes(P>0.05).Compared with the normal group,the model group had reduced weight and increased NSS(P<0.01).HE staining showed that there was brain tissue structure disorder,abundant necrotic neurons,cell swelling and interstitial edema of the scattered living nerve cells,destruction of mucosal integrity,disorder of intestinal gland arrangement,widening of intestinal space and mucosal edema in the model group.Compared with those in the normal group,the expression of IL-1βin brain and colon tissue and the serum IL-1βlevel in the model group significantly increased(P<0.01).The Shannon and Simpson diversity indexes in the model group decreased;the relative abundance of Firmicutes and Spirochetes decreased,while the abundance of Bacteroidetes,Proteobacteria,Elusimicrobia

关 键 词：重型颅脑损伤 小承气汤 肠道菌群 炎症反应 

分 类 号：R285.5[医药卫生—中药学]