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芍药苷通过上调血红素加氧酶-1 减轻 CCl4 诱导的肝纤维化小鼠的氧化应激、炎症和肝星状细胞激活。

Paeoniflorin modulates oxidative stress, inflammation and hepatic stellate cells activation to alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1 in mice.

机构信息

Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Pharmacology, Chongqing Medical University, Chongqing, China.

出版信息

J Pharm Pharmacol. 2021 Mar 6;73(3):338-346. doi: 10.1093/jpp/rgaa042.

Abstract

OBJECTIVES

The role of Paeoniflorin on hepatic fibrosis and the specific mechanisms has not yet been elucidated. Therefore, we explored whether Paeoniflorin exerted protective effects on carbon tetrachloride (CCl4)-induced hepatic fibrosis and the underlying mechanisms.

METHODS

A model of hepatic fibrosis was induced by intraperitoneally injecting with CCl4 (10% 5 μl/g) twice a week for 7 weeks. To explore the effects of Paeoniflorin, mice were treated with Paeoniflorin (100 mg/kg) by gavage once a day at 1 week after modeling until they were sacrificed.

KEY FINDINGS

Paeoniflorin remarkably improved liver function and histopathological changes of hepatic tissues in CCl4-induced liver injury. Besides, the serum MAO enzyme activity and hydroxyproline contents were notably decreased following the intervention of Paeoniflorin. The decreased expression of Vimentin, α-SMA, Col1a and Desmin manifested the inhibition of the hepatic stellate cells (HSCs) activation. Interestingly, Paeoniflorin intervention significantly upregulated the expression of heme oxygenase-1, and attenuated the inflammatory cytokines production as well as the CCl4-induced oxidative stress imbalance.

CONCLUSIONS

Paeoniflorin could effectively alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1, and it might be a new effective option for the comprehensive treatment of hepatic fibrosis.

摘要

目的

芍药苷对肝纤维化的作用及其具体机制尚不清楚。因此,我们探讨了芍药苷是否对四氯化碳(CCl4)诱导的肝纤维化具有保护作用及其潜在机制。

方法

通过每周两次腹腔注射 10% CCl4(5μl/g),建立肝纤维化模型,共 7 周。为了探讨芍药苷的作用,在建模后 1 周开始,每天通过灌胃给予芍药苷(100mg/kg)进行干预,直至处死。

主要发现

芍药苷显著改善了 CCl4 诱导的肝损伤小鼠的肝功能和肝组织的组织学变化。此外,芍药苷干预后血清 MAO 酶活性和羟脯氨酸含量明显降低。Vimentin、α-SMA、Col1a 和 Desmin 的表达减少表明肝星状细胞(HSCs)的激活受到抑制。有趣的是,芍药苷干预显著上调血红素加氧酶-1 的表达,减轻了 CCl4 诱导的炎症细胞因子产生和氧化应激失衡。

结论

芍药苷通过上调血红素加氧酶-1 有效缓解 CCl4 诱导的肝纤维化,可能是肝纤维化综合治疗的一种新的有效选择。

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