Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats.
Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats.
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DOI：
10.3389/fphar.2018.00709
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发表时间：
2018
影响因子：
5.6
通讯作者：
Sakamoto N
中科院分区：
文献类型：
--
作者：
Ohara M;Ohnishi S;Hosono H;Yamamoto K;Fu Q;Maehara O;Suda G;Sakamoto N
背景：肝纤维化是一个复杂的炎症和纤维化过程，纤维化的进展导致肝硬化。唯一的治疗方法是去除有害刺激和肝移植。因此，需要开发抗纤维化疗法。棕榈酰乙醇胺（PEA）是一种内源性脂肪酸酰胺，属于N-酰基乙醇胺家族，存在于蛋黄和花生等食物中。PEA具有治疗性抗炎、镇痛和神经保护作用。然而，PEA在肝纤维化中的作用和作用仍然未知。在这里，我们研究了PEA在大鼠肝纤维化中的治疗作用。方法：采用体外实验研究PEA对肝星状细胞（HSCs，LX-2）活化的影响。腹腔注射50%四氯化碳1.5mL/kg，每周2次，共4周，诱导肝纤维化。从第3周开始，每周三次腹腔注射PEA（20 mg/kg），持续2周。然后处死大鼠，我们进行了组织学和定量逆转录聚合酶链反应分析。结果：PEA可显著下调转化生长因子β1诱导的HSC α-平滑肌肌动蛋白（SMA）的表达。PEA以剂量依赖方式抑制TGF-β1诱导的SMAD 2磷酸化，上调SMAD 7表达。报告基因分析表明，PEA下调TGF-β1上调的SMAD复合物的转录活性。PEA能显著减少肝纤维化大鼠的纤维化面积、I型胶原沉积、HSC和枯否细胞的活化。结论：PEA通过抑制TGF-β1/SMAD信号通路，抑制HSC的活化。PEA的给药在大鼠肝纤维化模型中产生了显著的改善，可能是通过抑制HSC和枯否细胞的活化。PEA可能是一种潜在的治疗肝纤维化的新方法。
Background: Liver fibrosis is a complex inflammatory and fibrogenic process, and the progression of fibrosis leads to cirrhosis. The only therapeutic approaches are the removal of injurious stimuli and liver transplantation. Therefore, the development of anti-fibrotic therapies is desired. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the N-acylethanolamines family and contained in foods such as egg yolks and peanuts. PEA has therapeutic anti-inflammatory, analgesic, and neuroprotective effects. However, the effects and roles of PEA in liver fibrosis remain unknown. Here we investigated the therapeutic effects of PEA in rats with liver fibrosis. Methods: We conducted in vitro experiments to investigate the effects of PEA on the activation of hepatic stellate cells (HSCs, LX-2). Liver fibrosis was induced by an intraperitoneal injection of 1.5 mL/kg of 50% carbon tetrachloride twice a week for 4 weeks. Beginning at 3 weeks, PEA (20 mg/kg) was intraperitoneally injected thrice a week for 2 weeks. Then rats were sacrificed and we performed histological and quantitative reverse-transcription polymerase chain reaction analyses. Results: The expression of α-smooth muscle actin (SMA) induced by transforming growth factor (TGF)-β1 in HSCs was significantly downregulated by PEA. PEA treatment inhibited the TGF-β1-induced phosphorylation of SMAD2 in a dose-dependent manner, and upregulated the expression of SMAD7. The reporter gene assay demonstrated that PEA downregulated the transcriptional activity of the SMAD complex upregulated by TGF-β1. Administration of PEA significantly reduced the fibrotic area, deposition of type I collagen, and activation of HSCs and Kupffer cells in rats with liver fibrosis. Conclusion: Activation of HSCs was significantly decreased by PEA through suppression of the TGF-β1/SMAD signaling pathway. Administration of PEA produced significant improvement in a rat model of liver fibrosis, possibly by inhibiting the activation of HSCs and Kupffer cells. PEA may be a potential new treatment for liver fibrosis.
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影响因子：
4.8
作者：
Han, YP;Zhou, L;Tsukamoto, H
通讯作者：
Tsukamoto, H
影响因子：
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作者：
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Cuzzocrea, Salvatore
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