Department of Gastrointestinal Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China.
Department of Neurology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China.
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12697. Epub 2022 Mar 24.
Aspirin reduces the liver fibrosis index and inflammation in patients and rats. However, the specific mechanism underlying the effects of aspirin are yet to be elucidated. The present study aimed to investigate the effects of aspirin on thioacetamide (TAA)‑induced liver fibrosis in rats and hepatic stellate cells (HSCs) via the TGF‑β1/Smad signaling pathway. Liver fibrosis was induced in Sprague Dawley rats by intraperitoneal injection of 200 mg/kg TAA twice weekly for 8 weeks. Aspirin (30 mg/kg) was administered to rats by gavage once every morning over a period of 8 weeks. Masson's trichrome and H&E staining were used to detect and analyze the pathological changes in liver tissues. Western blot analysis and immunohistochemistry were applied to determine the protein expression levels of α‑smooth muscle actin (α‑SMA), collagen I, TGF‑β1, phosphorylated (p)‑Smad2 and p‑Smad3. In addition, reverse transcription‑quantitative PCR was performed to detect the mRNA expression levels of α‑SMA, collagen type I α 1 chain (COL1A1) and TGF‑β1. The results demonstrated that treatment with aspirin significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hydroxyproline in the TAA + aspirin compared with that in the TAA group. In the rat liver fibrosis model, pathological changes in liver tissues were improved following treatment with aspirin. Similarly, a marked decrease was observed in protein expression levels of α‑SMA, collagen I, TGF‑β1, p‑Smad2 and p‑Smad3. Furthermore, aspirin administration decreased the mRNA levels of α‑SMA, COL1A1 and TGF‑β1. In addition, HSCs were treated with different concentrations of aspirin (10, 20 and 40 mmol/l), and the protein expression levels of α‑SMA, collagen I, TGF‑β1, p‑Smad2 and p‑Smad3 were reduced in a dose‑dependent manner. Overall, the present study showed that aspirin attenuated liver fibrosis and reduced collagen production by suppressing the TGF‑β1/Smad signaling pathway, thus revealing a potential mechanism of aspirin in the treatment of liver fibrosis.
阿司匹林可降低患者和大鼠的肝纤维化指标和炎症。然而，阿司匹林作用的确切机制仍有待阐明。本研究旨在通过 TGF-β1/Smad 信号通路探讨阿司匹林对硫代乙酰胺（TAA）诱导的大鼠肝纤维化和肝星状细胞（HSCs）的影响。通过每周两次腹腔注射 200mg/kg TAA 8 周诱导 Sprague Dawley 大鼠肝纤维化。阿司匹林（30mg/kg）通过灌胃给药，每天早上一次，持续 8 周。采用 Masson 三色和 H&E 染色检测和分析肝组织的病理变化。采用 Western blot 分析和免疫组化法测定α-平滑肌肌动蛋白（α-SMA）、I 型胶原、TGF-β1、磷酸化（p）-Smad2 和 p-Smad3 的蛋白表达水平。此外，采用逆转录-定量 PCR 检测 α-SMA、I 型胶原α1 链（COL1A1）和 TGF-β1 的 mRNA 表达水平。结果表明，与 TAA 组相比，TAA+阿司匹林组的血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和羟脯氨酸水平明显降低。在大鼠肝纤维化模型中，阿司匹林治疗后肝组织的病理变化得到改善。同样，α-SMA、I 型胶原、TGF-β1、p-Smad2 和 p-Smad3 的蛋白表达水平也明显下降。此外，阿司匹林给药降低了 α-SMA、COL1A1 和 TGF-β1 的 mRNA 水平。此外，用不同浓度的阿司匹林（10、20 和 40mmol/l）处理 HSCs，α-SMA、I 型胶原、TGF-β1、p-Smad2 和 p-Smad3 的蛋白表达水平呈剂量依赖性降低。综上所述，本研究表明，阿司匹林通过抑制 TGF-β1/Smad 信号通路减轻肝纤维化和减少胶原产生，从而揭示了阿司匹林治疗肝纤维化的潜在机制。
