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三七皂苷通过抑制Jak2/Stat3信号通路改善实验性肝纤维化和肝星状细胞增殖。

Panax notoginseng saponins ameliorates experimental hepatic fibrosis and hepatic stellate cell proliferation by inhibiting the Jak2/ Stat3 pathways.

作者信息

Hui Jiang, Gao Jiarong, Wang Yongzhong, Zhang Jiafu, Han Yanquan, Wei Liangbing, Wu Jian

出版信息

J Tradit Chin Med. 2016 Apr;36(2):217-24. doi: 10.1016/s0254-6272(16)30030-9.

DOI:10.1016/s0254-6272(16)30030-9
PMID:27400477
Abstract

OBJECTIVE

To investigate the inhibitory effect of Panax notoginseng saponins (PNS) on liver fibrosis and explore the underlying mechanisms.

METHODS

Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. The effect of PNS on CCl4-induced liver fibrosis was studied with histochemical and biochemical analysis. Transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and collagen I mRNA expression were determined by reverse transcripwhile, the protein expression levels of α-SMA, collagen I, phosphorylation-Janus activated kinase signal transducer (p-Jak2)/Jak2, and phosphorylation-activator of transcription (p-Stat)3/Stat3 were determined by immunohistochemistry and/or immunoblotting.

RESULTS

PNS treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase and aspartate aminotransferase. Histopathological results indicated that PNS alleviated liver damage and reduced the formation of fibrous septa. Moreover, PNS significantly decreased liver hydroxyproline and significantly attenuated expressions of collagen I, α-SMA, TGF-β1, p-Jak2 / Jak2, and p-Stat3/Stat3 in the rat liver fibrosis model and HSCs.

CONCLUSION

PNS can relieve liver fibrosis by modulating Jak2/Stat3 signaling transduction pathway, which may be one of its mechanisms to suppress hepatic fibrosis.

摘要

目的

研究三七总皂苷(PNS)对肝纤维化的抑制作用并探讨其潜在机制。

方法

采用四氯化碳(CCl4)处理的大鼠和肝星状细胞(HSCs)。通过组织化学和生化分析研究PNS对CCl4诱导的肝纤维化的影响。采用逆转录法测定转化生长因子(TGF)-β1、α-平滑肌肌动蛋白(α-SMA)和I型胶原mRNA的表达,同时采用免疫组织化学和/或免疫印迹法测定α-SMA、I型胶原、磷酸化- Janus活化激酶信号转导子(p-Jak2)/Jak2和磷酸化-信号转导和转录激活子(p-Stat)3/Stat3的蛋白表达水平。

结果

PNS处理显著改善了大鼠的肝功能,表现为血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性降低。组织病理学结果表明,PNS减轻了肝损伤并减少了纤维间隔的形成。此外,PNS显著降低了大鼠肝纤维化模型和HSCs中肝羟脯氨酸含量,并显著减弱了I型胶原、α-SMA、TGF-β1、p-Jak2 / Jak2和p-Stat3/Stat3的表达。

结论

PNS可通过调节Jak2/Stat3信号转导通路缓解肝纤维化,这可能是其抑制肝纤维化的机制之一。

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