扶正化瘀方抗大鼠肝纤维化的代谢机制。
Metabolic mechanisms of Fuzheng-Huayu formula against liver fibrosis in rats.
机构信息
Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, china.
出版信息
J Ethnopharmacol. 2019 Jun 28;238:111888. doi: 10.1016/j.jep.2019.111888. Epub 2019 Apr 17.
ETHNOPHARMACOLOGICAL RELEVANCE
Fuzheng-Huayu formula (FZHY) is traditionally used to treat liver fibrosis in clinic. The study was conducted to investigate the metabolic mechanisms of FZHY against liver fibrosis in rats.
MATERIALS AND METHODS
Rats with CCl -induced liver fibrosis were treated with FZHY and its components, including amygdalin, cordyceps polysaccharide and gypenoside, respecitively. Liver fibrosis and function were assesed by histopathological examination, Western blot and serum biochemical detection. Metabolic profiling of liver tissue, serum and urine in each group were detected by gas chromatography-mass spectrometry (GC-MS) and transcriptomic changes were tested by gene chip. RT-qPCR was used to validate levels of different expressed genes (DEGs) with statistical significance. Metabolic network together with DEGs was constructed based on KEGG database.
RESULTS
FZHY effectively improved liver fibrosis better than the mixture or single use of gypenoside, cordyceps sinensis mycelia and amygdalin. FZHY treatment widely modulated the metabolic profiles perturbed by liver fibrosis, involving several important metabolic pathways, including glycolysis/gluconeogenesis, glucose-alanine cycle, citrate cycle, galactose metabolism, tryptophan metabolism, urea cycle, etc. It also increased alanine and decreased glucose levels in liver tissue and decreased both of them in serum and urine, which were dysregulated by CCl treatment. Additionally, FZHY also upregulated expression of metabolic enzymes including Hk2, Adh1 and Gpt increased, and downregulated Gs and Acss2.
CONCLUSION
FZHY improved liver fibrosis in rats via altering the metabolic pathways and regulating gene expression of involved metabolic enzymes.
民族药理学相关性
扶正化瘀方（FZHY）传统上用于临床治疗肝纤维化。本研究旨在探讨 FZHY 对 CCl4 诱导的大鼠肝纤维化的代谢机制。
材料和方法
用 FZHY 及其成分（包括苦杏仁苷、虫草多糖和绞股蓝总苷）分别处理 CCl4 诱导的肝纤维化大鼠。通过组织病理学检查、Western blot 和血清生化检测评估肝纤维化和肝功能。用气相色谱-质谱联用（GC-MS）检测各组肝组织、血清和尿液的代谢谱，用基因芯片检测转录组变化。用 RT-qPCR 验证具有统计学意义的不同表达基因（DEGs）的水平。根据 KEGG 数据库构建代谢网络和 DEGs。
结果
FZHY 能有效改善肝纤维化，优于绞股蓝总苷、虫草菌丝体和苦杏仁苷的混合物或单一使用。FZHY 治疗广泛调节了由肝纤维化引起的代谢谱紊乱，涉及几个重要的代谢途径，包括糖酵解/糖异生、葡萄糖-丙氨酸循环、柠檬酸循环、半乳糖代谢、色氨酸代谢、尿素循环等。它还增加了肝组织中丙氨酸和降低了葡萄糖水平，降低了血清和尿液中的两者水平，这是 CCl4 处理失调的。此外，FZHY 还上调了代谢酶的表达，包括 Hk2、Adh1 和 Gpt 增加，下调了 Gs 和 Acss2。
结论
FZHY 通过改变代谢途径和调节参与代谢酶的基因表达来改善大鼠肝纤维化。
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