Zhao Jindong, Liu Lili, Xin Ling, Lu Yunxia, Yang Xiaojun, Hou Yong, Shi Mei, Han Sha, Zhou Hao, Liu Yonghua, Fang Zhaohui, Li Yan, Zhang Guoliang
Graduate School, Anhui University of Chinese Medicine, Hefei 230012, China.
Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China.
Evid Based Complement Alternat Med. 2022 Jan 13;2022:6611563. doi: 10.1155/2022/6611563. eCollection 2022.
The aim of this study was to evaluate the effects of a modified Xiaohua Funing decoction (Xfd) on acute liver failure (ALF) and determine whether the protective mechanisms are related to alterations in the gut microbiota.
An animal model of ALF was induced by intraperitoneal injection of D-galactosamine (D-Gal, 0.5 g/kg) and lipopolysaccharide (LPS, 100 g/kg). Male BALB/ mice were randomly divided into the following 4 groups: the control group (saline, Con), model group (D-Gal/LPS, Mod), silymarin pretreatment group (200 mg/kg, Sil), and modified Xfd pretreatment group (650 mg/kg, Xfd). The Sil and Xfd groups received the respective intervention orally for 14 days and 2 h before D-Gal/LPS treatment. The liver injury markers included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver histology. 16S rRNA gene sequencing was performed to assess the effects on the caecum content.
D-Gal/LPS treatment caused severe ALF, illustrating that the ALF model was successfully established. The administration of Sil and Xfd greatly reduced the serum ALT and AST levels and improved the pathological signs of liver injury. However, no significant difference was found between the two groups. In contrast to the Mod group, the Sil and Xfd groups showed a shift toward the Con group in terms of the gut microbiota structure. The abundances of Firmicutes and Bacteroidetes and the Bacteroidetes/Firmicutes ratio in the Mod group significantly differed from those in the Con group. The Sil and Xfd groups showed restoration of the disordered microbiota. Significantly increased relative abundances of Lachnospiraceae_NK4A136_group and Candidatus_Saccharimonas and a markedly decreased Muribaculaceae abundance were found in the Sil and Xfd mice compared with those in the Mod mice ( < 0.01, < 0.05). Interestingly, a negative correlation was observed between the abundances of the gut microbiota constituents, specifically Clostridia_UCG-014, and ALT and AST levels.
In summary, our results indicate that Xfd may protect the liver and modify the gut microbiota in ALF mice.
本研究旨在评估改良的小华茯苓汤（Xfd）对急性肝衰竭（ALF）的影响，并确定其保护机制是否与肠道微生物群的改变有关。
通过腹腔注射D-半乳糖胺（D-Gal，0.5 g/kg）和脂多糖（LPS，100 g/kg）诱导建立ALF动物模型。雄性BALB/c小鼠随机分为以下4组：对照组（生理盐水，Con）、模型组（D-Gal/LPS，Mod）、水飞蓟素预处理组（200 mg/kg，Sil）和改良Xfd预处理组（650 mg/kg，Xfd）。Sil组和Xfd组在D-Gal/LPS处理前14天和2小时分别口服相应干预药物。肝损伤标志物包括丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平以及肝脏组织学。进行16S rRNA基因测序以评估对盲肠内容物的影响。
D-Gal/LPS处理导致严重的ALF，表明成功建立了ALF模型。Sil和Xfd给药显著降低了血清ALT和AST水平，并改善了肝损伤的病理体征。然而，两组之间未发现显著差异。与Mod组相比，Sil组和Xfd组在肠道微生物群结构方面向Con组转变。Mod组中厚壁菌门和拟杆菌门的丰度以及拟杆菌门/厚壁菌门的比例与Con组显著不同。Sil组和Xfd组显示紊乱的微生物群得以恢复。与Mod组小鼠相比，Sil组和Xfd组小鼠中Lachnospiraceae_NK4A136_group和Candidatus_Saccharimonas的相对丰度显著增加，而Muribaculaceae的丰度显著降低（<0.01，<0.05）。有趣的是，观察到肠道微生物群成分（特别是Clostridia_UCG-014）的丰度与ALT和AST水平之间存在负相关。
总之，我们的结果表明Xfd可能对ALF小鼠的肝脏具有保护作用并改变其肠道微生物群。
