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.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Jul;35(7):690-695. doi: 10.3760/cma.j.cn121430-20230222-00104.
To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites.
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.
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, and α diversity 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.
Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.
探讨血必净注射液通过调节肠道微生物群及其代谢产物对脓毒症炎症的影响。
将45只雄性Sprague-Dawley（SD）大鼠随机分为假手术组（假手术组）、盲肠结扎穿孔（CLP）诱导的脓毒症组（CLP组）和血必净干预组（XBJ组，CLP术后1小时腹腔注射4 mL/kg血必净注射液），每组15只。观察术后24小时大鼠存活情况并进行处死。收集粪便进行16S rRNA基因测序和液相色谱-质谱联用（LC-MS）分析。
术后24小时，假手术组大鼠全部存活，XBJ组大鼠死亡率低于CLP组[47%（7/15）对60%（9/15），P>0.05]。与假手术组相比，CLP组肠道微生物群多样性降低，优势菌群改变，炎症相关菌群丰度增加。血必净改善了脓毒症引起的肠道微生物群变化，α多样性呈增加趋势（Ace指数：406.0±22.5对363.2±38.2，Chao1指数：409.7±21.8对362.4±42.5，均P>0.05）。限制性约束主坐标分析（cPCoA）显示同一组大鼠肠道微生物群具有高度相似性。CLP组以拟杆菌门为主，而假手术组和XBJ组以厚壁菌门为主。此外，与CLP组相比，血必净治疗增加了脓毒症大鼠有益菌的丰度，如疣微菌门、阿克曼氏菌和乳酸杆菌。LC-MS和正交偏最小二乘法判别分析（OPLS-DA）显示三组间有12种主要差异代谢产物，这些代谢产物之间存在一定相关性，与氨基酸和脂质代谢有关。相关性分析显示代谢产物变化与微生物群落之间存在显著相关性。
血必净可提高脓毒症大鼠的存活率，调节肠道菌群组成及相关代谢产物，为血必净治疗脓毒症提供了新的病理生理机制。
