Wang Li, Cui Huantian, Li Yuting, Cao Min, Man Shanshan, Guo Liying, Miao Jing, Jia Jianwei, Bian Yuhong, Zhang Zhaiyi
Tianjin Second People's Hospital, Tianjin, China.
Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.
Evid Based Complement Alternat Med. 2020 Oct 20;2020:8890182. doi: 10.1155/2020/8890182. eCollection 2020.
Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of and and decreased the relative abundance of and . However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.
抗纤丸（KX）已被临床用于治疗慢性肝损伤（CHI）。然而，KX治疗CHI的机制尚不清楚。本研究的目的主要集中在基于调节肠道微生物群和肠道通透性的CHI小鼠模型中KX的抗炎作用。我们首先使用四氯化碳（CCl）建立CHI模型并用KX进行治疗。还研究了KX对CHI模型小鼠的抗炎作用以及KX治疗后肠道通透性的变化。采用16S rRNA分析研究KX治疗后肠道微生物群组成的变化。此外，使用抗生素组合清除肠道微生物群，以进一步证实KX可通过调节肠道微生物群抑制炎症反应并降低肠道通透性来治疗CHI。结果表明，KX治疗显著改善了CHI模型小鼠的肝功能。KX还可增加结肠中紧密连接蛋白的水平，并降低肝脏中促炎细胞因子的表达。16S rRNA分析表明，KX治疗影响了CHI模型小鼠的α和β多样性。对16S rRNA测序的进一步分析表明，KX治疗在门水平上增加了厚壁菌门与拟杆菌门的比例。在属水平上，KX治疗增加了 和 的相对丰度，并降低了 和 的相对丰度。然而，清除肠道微生物群后，KX无法缓解CHI。清除肠道微生物群后，KX对肠道通透性和肝脏炎症反应的影响也降低了。总之，我们目前的研究表明，在CHI进展过程中肠道微生物群受到显著影响。KX可通过调节肠道微生物群抑制CHI模型小鼠的炎症反应并降低肠道通透性。
