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黑果腺肋花楸多糖通过 TGF-β1 介导的 PI3K/AKT 通路激活和调节肠道微生物群改善肝纤维化。

Aronia melanocarpa polysaccharide ameliorates liver fibrosis through TGF-β1-mediated the activation of PI3K/AKT pathway and modulating gut microbiota.

机构信息

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China.

College of Chinese Traditional Medicine, Jilin Agricultural Science and Technology University, Jilin 132101, China.

出版信息

J Pharmacol Sci. 2022 Dec;150(4):289-300. doi: 10.1016/j.jphs.2022.10.001. Epub 2022 Oct 4.

Abstract

The purpose of this experiment was to investigate the anti-hepatic fibrosis effect of Aronia melanocarpa polysaccharide (AMP) on TAA-induced liver fibrosis mice and its mechanism, as well as the changes in intestinal flora in vivo. This was established with a dose of 200 mg/kg TAA (i.p) once every three days, lasting for eight weeks. Colchicine with 0.4 mg/kg, and AMP (200 and 400 mg/kg) were given by intragastric administration (i.g) after 28 days of intraperitoneal injection of TAA. AMP treatment significantly inhibited the activities of liver injury markers ALT and AST in serum. Histopathological staining demonstrated that AMP significantly reversed TAA-induced hepatocyte necrosis and collagen deposition. In addition, AMP treatment block TGF- β1/Smads pathway inhibited the production of ECM and alleviates liver fibrosis. Furthermore, AMP treatment enhanced the phosphorylation of PI3K/AKT and decreased the expression of its downstream apoptosis-related proteins in liver, thus effectively alleviating TAA-induced liver fibrosis. In addition, 16S rDNA gene sequencing analysis showed that AMP treatment helped restore the imbalanced ecosystem of gut microbes, increased the proportion of Bacteroidetes and Proteobacteria, and increased species richness. Above findings clearly show that AMP is an effective method for treating liver fibrosis, possibly by improving the gut microbiota.

摘要

本实验旨在研究黑果腺肋花楸多糖(AMP)对 TAA 诱导的肝纤维化小鼠的抗肝纤维化作用及其机制,以及体内肠道菌群的变化。采用 200mg/kg TAA(腹腔注射),每三天一次,持续 8 周的剂量建立模型。28 天后,用秋水仙碱 0.4mg/kg 和 AMP(200 和 400mg/kg)灌胃给药。AMP 治疗显著抑制了血清中肝损伤标志物 ALT 和 AST 的活性。组织病理学染色表明,AMP 显著逆转了 TAA 诱导的肝细胞坏死和胶原沉积。此外,AMP 治疗通过抑制 ECM 的产生和减轻肝纤维化,阻断了 TGF-β1/Smads 通路。此外,AMP 治疗还能有效减轻 TAA 诱导的肝纤维化,增加肝脏中 PI3K/AKT 的磷酸化,并降低其下游凋亡相关蛋白的表达。此外,16S rDNA 基因测序分析表明,AMP 治疗有助于恢复肠道微生物失衡的生态系统,增加拟杆菌门和变形菌门的比例,并增加物种丰富度。这些发现清楚地表明,AMP 是一种治疗肝纤维化的有效方法,可能通过改善肠道微生物群。

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