Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Gastroenterology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210001, China.
Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Ethnopharmacol. 2021 Nov 15;280:114411. doi: 10.1016/j.jep.2021.114411. Epub 2021 Jul 12.
Acute-on-chronic liver failure (ACLF) is a key complication of chronic hepatitis, with a relatively high mortality rate and limited treatment options, which dramatically threatens human lives. Yi-Qi-Jian-Pi formula (YQJPF) is a herbal compound commonly used to treat liver failure.
The purpose of this research is to discuss the potential molecular biological effect and mechanism of YQJPF in ACLF.
In this study, we created a rat model of ACLF by CCl-, LPS- and D-Galactosamine (D-Gal) and an in vitro model of LPS-induced hepatocyte damage. The specific components of YQJPF and potential mechanism were explored based on bioinformatics analyses. Furthermore, we verified the effect of YQJPF on ACLF using immunohistochemistry, RT-qPCR, western blotting, and flow cytometry.
Our research demonstrated that, after YQJPF treatment, hepatocyte injury in rats was relieved. Bioinformatics analysis showed that PI3K/AKT, HIF-1, mitochondrial apoptosis pathways played prominent roles. YQJPF promoted HIF-1α protein expression and exerted protective effects against hypoxic injury, simultaneously reducing mitochondrial ROS production, suppressing hepatocyte apoptosis. Furthermore, we showed that YQJPF accelerates PI3K/AKT pathway activation, a known broad-spectrum inhibitor of PI3K. LY294002, which was used for reverse verification, suppressed the effect of YQJPF on hypoxic injury and ROS-mediated hepatocyte apoptosis.
YQJPF ameliorates liver injury by suppressing hypoxic injury and ROS-mediated hepatocyte apoptosis by modulating the PI3K/AKT pathway.
慢性肝炎的关键并发症是慢加急性肝衰竭（ACLF），其死亡率相对较高，治疗选择有限，严重威胁着人类的生命。益七健脾方（YQJPF）是一种常用于治疗肝衰竭的草药复方。
本研究旨在探讨 YQJPF 在 ACLF 中的潜在分子生物学作用和机制。
本研究通过 CCl4、LPS 和 D-半乳糖胺（D-Gal）构建大鼠 ACLF 模型和 LPS 诱导的肝细胞损伤体外模型，利用生物信息学分析探讨 YQJPF 的潜在作用机制，并通过免疫组化、RT-qPCR、Western blot 和流式细胞术验证 YQJPF 对 ACLF 的作用。
本研究表明，YQJPF 治疗后大鼠肝细胞损伤得到缓解。生物信息学分析表明，PI3K/AKT、HIF-1、线粒体凋亡途径发挥了重要作用。YQJPF 促进 HIF-1α 蛋白表达，发挥抗缺氧损伤作用，同时减少线粒体 ROS 产生，抑制肝细胞凋亡。此外，我们还表明，YQJPF 加速了 PI3K/AKT 通路的激活，这是一种广泛的 PI3K 抑制剂。用于反向验证的 LY294002 抑制了 YQJPF 对缺氧损伤和 ROS 介导的肝细胞凋亡的作用。
YQJPF 通过抑制缺氧损伤和 ROS 介导的肝细胞凋亡，调节 PI3K/AKT 通路改善肝损伤。
