血必净注射液对脓毒症大鼠肠道菌群及其代谢组学的积极影响  

Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats

作　　者：丁显飞 原阳阳 仝然 王坤[2] 刘韶华[1] 祁雪颜 张晓娟[1] 曹杰斌[3] 孙同文[1] Ding Xianfei;Yuan Yangyang;Tong Ran;Wang Kun;Liu Shaohua;Qi Xueyan;Zhang Xiaojuan;Cao Jiebin;Sun Tongwen(General ICU,the First Affiliated Hospital of Zhengzhou University,Henan Key Laboratory of Critical Care Medicine,Zhengzhou Key Laboratory of Sepsis,Henan Engineering Research Center for Critical Care Medicine,Zhengzhou 450052,Henan,China;Department of Anesthesiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan,China;Center for Disease Control and Prevention of Zhengzhou Erqi District,Changyun Institute,Zhengzhou 450052,Henan,China)

机构地区：[1]郑州大学第一附属医院综合ICU,河南省重症医学重点实验室,郑州市脓毒症重点实验室,河南省重症医学工程研究中心,郑州450052 [2]郑州大学第一附属医院麻醉科,郑州450052 [3]郑州市二七区疾病预防控制中心,长云(河南)医学检验实验室,郑州450052

出　　处：《中华危重病急救医学》2023年第7期690-695,共6页Chinese Critical Care Medicine

基　　金：国家自然科学基金(U2004110, 82172129, 82202370);河南省自然科学基金优秀青年基金项目(232300421048)。

摘　　要：目的探讨血必净注射液通过调节肠道菌群及其代谢物发挥改善脓毒症炎症的作用。方法将45只雄性SD大鼠随机分为假手术组(Sham组)、盲肠结扎穿孔术(CLP)诱导脓毒症组(CLP组)和血必净干预组(XBJ组,CLP术后1 h腹腔注射血必净注射液4 mL/kg),每组15只。于术后24 h观察大鼠存活情况并处死,收集粪便行16S rRNA基因测序和液相色谱-质谱(LC-MS)分析。结果术后24 h,Sham组大鼠均存活,XBJ组大鼠死亡率低于CLP组〔47%(7/15)比60%(9/15),P>0.05〕。与Sham组比较,CLP组肠道菌群多样性呈下降趋势,优势菌群发生变化,炎症相关菌群丰度增加。血必净改善了脓毒症引起的肠道菌群变化,α多样性有升高趋势(Ace指数:406.0±22.5比363.2±38.2,Chao1指数:409.7±21.8比362.4±42.5,均P>0.05);限制性主坐标分析(cPCoA)显示,同组大鼠间肠道菌群的相似性非常高。CLP组以拟杆菌门为优势门,而Sham组和XBJ组以厚壁菌门为优势门;此外,与CLP组相比,血必净治疗可增加脓毒症大鼠体内有益菌疣微菌门、阿克曼菌科、乳酸杆菌科的丰度。LC-MS和正交偏最小二乘判别分析(OPLS-DA)显示,3组大鼠间存在12种主要差异性代谢物,且这些代谢物之间具有一定相关性,与氨基酸和脂类代谢有关。相关性分析表明,代谢物与菌群的变化之间存在显著相关。结论血必净注射液可提高脓毒症大鼠存活率,调节肠道菌群及其相关代谢物,为血必净治疗脓毒症提供了一种新的病理生理机制。Objective To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites.Methods A total of 45 male Sprague-Dawley(SD)rats were randomly divided into Sham operation group(Sham group),cecal ligation and perforation(CLP)induced sepsis group(CLP group),and Xuebijing intervention group(XBJ group,4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP),with 15 rats in each group.The survival of rats was observed at 24 hours after operation and sacrificed.Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry(LC-MS)analysis.Results At 24 hours after operation,all rats in the Sham group survived,the mortality of rats in the XBJ group was lower than that in the CLP group[47%(7/15)vs.60%(9/15),P>0.05].Compared with the Sham group,the diversity of gut microbiota in the CLP group decreased,the dominant flora changed,and the abundance of inflammation-related flora increased.Xuebijing improved the changes in gut microbiota caused by sepsis,andαdiversity showed an increasing trend(Ace index:406.0±22.5 vs.363.2±38.2,Chao1 index:409.7±21.8 vs.362.4±42.5,both P>0.05).Restrictive constrained principal coordinate analysis(cPCoA)showed a high similarity in gut microbiota among the same group of rats.The CLP group was dominated by Bacteroidetes,while the Sham and XBJ groups were dominated by Firmicutes.In addition,compared with the CLP group,Xuebijing treatment increased the abundance of beneficial bacteria in septic rats,such as Verrucomicrobia,Akkermansia and Lactobacillus.LC-MS and orthogonal partial least squares discriminant analysis(OPLS-DA)showed that there were 12 main differential metabolites among the three groups,and there were certain correlations between these metabolites,which were related to amino acid and lipid metabolism.Correlation analysis showed a significant correlation between changes in metabolites and microbial communities.Conclusion Xuebijing can improve the survival rate of septi

关 键 词：血必净 脓毒症 肠道菌群 代谢组学 

分 类 号：R459.7[医药卫生—急诊医学]