通过靶向 PI3K/Akt/mTOR 通路抑制肝纤维化和肝星状细胞活化

IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Molecular medicine reports Pub Date : 2024-11-01 Epub Date: 2024-09-02 DOI:10.3892/mmr.2024.13314
Zhiheng Dong, Haibin Guan, Lu Wang, Lijuan Liang, Yifan Zang, Lan Wu, Lidao Bao
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引用次数: 0

摘要

肝纤维化(HF)是几种慢性肝病进展过程中出现的一个过程,目前尚缺乏有效的治疗方案。中药或蒙药中经常使用麝香草苷(CTL)来治疗肝病。然而,其作用机制仍不清楚。在本研究中,CTL 被用于治疗 CCl4 诱导的高频肝病大鼠。研究分析了大鼠肝脏的组织病理学、生化和高频标志物,并用CTL注入的血清治疗肝星状细胞(HSCs),以检测HSC活化的相关标志物。检测了体外和体内的蛋白质表达途径。组织病理学结果显示,CTL能明显改善CCl4诱导的肝损伤,降低天冬氨酸氨基转移酶和丙氨酸氨基转移酶水平,促进E-cadherin的表达,降低α-平滑肌肌动蛋白(SMA)、SOX9、胶原蛋白I和羟脯氨酸的表达。此外,还发现注入 CTL 的血清可降低造血干细胞中 α-SMA 和胶原 I 的表达。进一步的研究表明,CTL 可抑制大鼠肝脏中 PI3K/Akt/mTOR 通路的活性。给造血干细胞注射PI3K激动剂740Y-P后,CTL对PI3K/Akt//mTOR通路的抑制作用被阻断。这些结果表明,CTL可通过抑制PI3K/Akt/mTOR途径来抑制高频和造血干细胞的活化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Carthamus tinctorius L. inhibits hepatic fibrosis and hepatic stellate cell activation by targeting the PI3K/Akt/mTOR pathway.

Hepatic fibrosis (HF) is a process that occurs during the progression of several chronic liver diseases, for which there is a lack of effective treatment options. Carthamus tinctorius L. (CTL) is often used in Chinese or Mongolian medicine to treat liver diseases. However, its mechanism of action remains unclear. In the present study, CTL was used to treat rats with CCl4‑induced HF. The histopathological, biochemical and HF markers of the livers of the rats were analyzed, and CTL‑infused serum was used to treat hepatic stellate cells (HSCs) in order to detect the relevant markers of HSC activation. Protein expression pathways were detected both in vitro and in vivo. Histopathological results showed that CTL significantly improved CCl4‑induced liver injury, reduced aspartate aminotransferase and alanine aminotransferase levels, promoted E‑cadherin expression, and decreased α‑smooth muscle actin (SMA), SOX9, collagen I and hydroxyproline expression. Moreover, CTL‑infused serum was found to decrease α‑SMA and collagen I expression in HSCs. Further studies showed that CTL inhibited the activity of the PI3K/Akt/mTOR pathway in the rat livers. Following the administration of the PI3K agonist 740Y‑P to HSCs, the inhibitory effect of CTL on the PI3K/Akt//mTOR pathway was blocked. These results suggested that CTL can inhibit HF and HSC activation by inhibiting the PI3K/Akt/mTOR pathway.

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来源期刊
Molecular medicine reports
Molecular medicine reports 医学-病理学
CiteScore
7.60
自引率
0.00%
发文量
321
审稿时长
1.5 months
期刊介绍: Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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