Prediction of Srebp-1 as a Key Target of Qing Gan San Against MAFLD in Rats via RNA-Sequencing Profile Analysis.
Prediction of Srebp-1 as a Key Target of Qing Gan San Against MAFLD in Rats via RNA-Sequencing Profile Analysis.
复制标题
通过 RNA 测序分析预测 Srebp-1 作为清肝散抗大鼠 MAFLD 的关键靶点
DOI：
10.3389/fphar.2021.680081
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Song X
中科院分区：
文献类型：
--
作者：
Yang B;Sun J;Liang S;Wu P;Lv R;He Y;Li D;Sun W;Song X
代谢相关脂肪性肝病(MAFLD)是世界范围内最常见的慢性肝病，中医药治疗该疾病日益受到重视。清肝散由黄精、陈皮、白桑叶、L叶、菊苣、乌拉尔甘草、茜草组成。本研究旨在揭示清肝颗粒对高脂饮食诱导的大鼠高脂血症的降脂、降脂作用及其机制。清肝颗粒能显著降低血清和肝组织中总胆固醇和甘油三酯的水平，并对肝功能有部分保护作用。此外，病理组织学观察显示，清肝颗粒可明显改善肝脏脂肪堆积，HE染色和油红O染色均证实了其作用。用RNA测序的方法进一步研究MAFLD发生和治疗过程中的关键基因。系统聚类分析显示，经清热解毒汤治疗后，MAFLD大鼠基因表达谱恢复到正常水平。QGS有222个与MAFLD相关的潜在治疗靶点。这些靶标的浓缩分析表明，QGS影响生物功能/途径，如调节脂质代谢过程(GO：0019216)和非酒精性脂肪性肝病途径(HSA04932)，并确定SREBP-1是胆固醇和甘油三酯合成的关键调节因子。随后，免疫荧光和Western印迹分析表明，QGS抑制了SREBP-1从细胞质向细胞核的转移，表明SREBP-1的激活受到抑制。本研究揭示了清肝颗粒治疗酒精性脂肪肝的作用机制，为进一步探讨酒精性脂肪肝的发病机制和中医治法提供了见解和展望。
Metabolism-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and the use of traditional Chinese medicines (TCMs) to treat this disease has attracted increasing attention. The Qing Gan San (QGS) formula comprises Polygonatum sibiricum, the peel of Citrus reticulata Blanco, the leaves of Morus alba L, Cichorium intybus, Glycyrrhiza uralensis Fisch, and Cirsium setosum. The present study aimed to uncover the anti-hyperlipidaemic effects, hepatic fat accumulation-lowering effects and mechanisms of QGS in high-fat diet-induced MAFLD rats. QGS significantly reduced the levels of total cholesterol and triglycerides in both serum and liver tissue and partially protected hepatic function. Additionally, QGS significantly ameliorated hepatic lipid accumulation with histopathology observation, as demonstrated by H&E and oil red O staining. RNA sequencing was used to further investigate the key genes involved in the development and treatment of MAFLD. Hierarchical clustering analysis showed that the gene expression profiles in rats with MAFLD were reversed to normal after QGS treatment. QGS had 222 potential therapeutic targets associated with MAFLD. Enrichment analysis among these targets revealed that QGS affected biological functions/pathways such as the regulation of lipid metabolic processes (GO: 0019216) and the non-alcoholic fatty liver disease pathway (hsa04932), and identified Srebp-1 as a key regulator in the synthesis of cholesterol and triglycerides. Subsequently, both immunofluorescence and Western blot analyses demonstrated that QGS suppressed the transfer of Srebp-1 to the nucleus from the cytoplasm, suggesting that the activation of Srebp-1 was inhibited. Our study reveals the effects and mechanisms of QGS in the treatment of MAFLD and provides insights and prospects to further explore the pathogenesis of MAFLD and TCM therapies.
登录
查看更多内容
影响因子：
2.2
作者：
Gou, San-hu;He, Miao;Ni, Jing-man
通讯作者：
Ni, Jing-man
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
3.8
作者：
Ko, Jong-Hee;Kwon, Hyuk-Sang;Kang, Jae-Hoon
通讯作者：
Kang, Jae-Hoon
通过网络药理学预测 VEGF-C 作为柑橘纯总黄酮对抗小鼠 NAFLD 的关键靶点
影响因子：
5.6
作者：
Hong, Wei;Li, Songsong;Chen, Zhiyun
通讯作者：
Chen, Zhiyun
DOI：
10.1038/nrgastro.2017.32
发表时间：
2017-06
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Gluchowski NL;Becuwe M;Walther TC;Farese RV Jr
通讯作者：
Farese RV Jr