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丹皮酚通过抑制 TGF-β/Smad3 信号通路抑制肝星状细胞活化缓解 CCl4 诱导的肝纤维化。

Paeonol alleviates CCl-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling.

机构信息

a Department of Anatomy , Chongqing Medical University , Chongqing , People's Republic of China.

b Department of Medical Laboratory , Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders , Chongqing , People's Republic of China.

出版信息

Immunopharmacol Immunotoxicol. 2019 Jun;41(3):438-445. doi: 10.1080/08923973.2019.1613427. Epub 2019 May 23.

DOI:10.1080/08923973.2019.1613427
PMID:31119954
Abstract

Paeonol is a natural phenolic component isolated from the root bark of peony with multiple pharmacological activities. We investigated the anti-fibrotic effect and underlying mechanism of paeonol. Twenty-four male C57BL/6J mice were divided into 4 groups ( = 6 in each group), injected with CCl to induce liver fibrosis and administrated with paeonol according to the regimen. The serum activity of ALT and AST, and H&E staining were to assess liver injury. Sirius and Masson staining, and hydroxyproline content were to evaluate the degree of liver fibrosis. TNF-α, IL-6, TGF-β, MDA, GSH-PX, SOD, and CAT were detected to reflect inflammation and oxidative stress. RT-qPCR and Western blot analysis to assess the activation of HSCs and TGF-β/Smad3 signaling. Paeonol ameliorated liver injury and liver fibrosis, reflected by the decrease of ALT, AST, less lesion in H&E staining, mitigated fibrosis in Sirius and Masson staining, lessened content of hydroxyproline. Paeonol attenuated the level of IL-6 and TNF-α, and elevated the activity of GSH-PX, SOD, and CAT with reducing the level of MDA. The expression of col 1a, α-SMA, vimentin, and desmin were down-regulated and TGF-β/Smad3 signaling pathway was inhibited. These data demonstrated that paeonol could alleviate CCl-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling.

摘要

丹皮酚是从牡丹根皮中分离得到的一种具有多种药理活性的天然酚类成分。我们研究了丹皮酚的抗纤维化作用及其机制。

将 24 只雄性 C57BL/6J 小鼠随机分为 4 组(每组 6 只),用 CCl 诱导肝纤维化,并按方案给予丹皮酚。检测血清 ALT 和 AST 活性、H&E 染色评估肝损伤;天狼星红和 Masson 染色、羟脯氨酸含量评估肝纤维化程度;TNF-α、IL-6、TGF-β、MDA、GSH-PX、SOD 和 CAT 检测反映炎症和氧化应激;RT-qPCR 和 Western blot 分析评估 HSCs 激活和 TGF-β/Smad3 信号通路。

丹皮酚改善了肝损伤和肝纤维化,表现为 ALT、AST 降低,H&E 染色病变减轻,天狼星红和 Masson 染色纤维化减轻,羟脯氨酸含量减少。丹皮酚降低了 IL-6 和 TNF-α 的水平,提高了 GSH-PX、SOD 和 CAT 的活性,降低了 MDA 的水平。Col 1a、α-SMA、波形蛋白和结蛋白的表达下调,TGF-β/Smad3 信号通路被抑制。

这些数据表明,丹皮酚通过抑制 TGF-β/Smad3 信号通路抑制肝星状细胞激活,可减轻 CCl 诱导的肝纤维化。

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