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依西美坦通过抑制肝星状细胞活化和促进白细胞介素 10 的分泌减轻大鼠肝纤维化。

Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10.

机构信息

Shanghai Medical College of Fudan University, Shanghai 200032, China.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

J Immunol Res. 2017;2017:3072745. doi: 10.1155/2017/3072745. Epub 2017 Dec 10.

Abstract

Exemestane (EXE) is an irreversible steroidal aromatase inhibitor mainly used as an adjuvant endocrine therapy for postmenopausal women suffering from breast cancer. Besides inhibiting aromatase activity, EXE has multiple biological functions, such as antiproliferation, anti-inflammatory, and antioxidant activities which are all involved in hepatic fibrosis. Therefore, we investigated the role of EXE during the progress of hepatic fibrosis. The effect of EXE on liver injury and fibrosis were assessed in two hepatic fibrosis rat models, which were induced by either carbon tetrachloride (CCl) or bile duct ligation (BDL). The influence of EXE treatment on activation and proliferation of primary rat hepatic stellate cells (HSCs) was observed . The results showed that EXE attenuated the liver fibrosis by decreasing the collagen deposition and -SMA expression and inhibited the activation and proliferation of primary rat HSCs . Additionally, EXE promoted the secretion of antifibrotic and anti-inflammatory cytokine IL-10 and in HSC-T6 culture media. In conclusion, our findings reveal a new function of EXE on hepatic fibrosis and prompted its latent application in liver fibrotic-related disease.

摘要

依西美坦(EXE)是一种不可逆的甾体芳香酶抑制剂,主要用作绝经后患有乳腺癌的女性的辅助内分泌治疗。除了抑制芳香酶活性外,EXE 还具有多种生物学功能,如抗增殖、抗炎和抗氧化活性,这些都与肝纤维化有关。因此,我们研究了 EXE 在肝纤维化进展过程中的作用。我们在两种肝纤维化大鼠模型中评估了 EXE 对肝损伤和纤维化的影响,这两种模型是由四氯化碳(CCl)或胆管结扎(BDL)诱导的。观察了 EXE 处理对原代大鼠肝星状细胞(HSCs)激活和增殖的影响。结果表明,EXE 通过减少胶原蛋白沉积和 -SMA 表达来减轻肝纤维化,并抑制原代大鼠 HSCs 的激活和增殖。此外,EXE 促进了抗纤维化和抗炎细胞因子 IL-10 在 HSC-T6 培养物中的分泌。总之,我们的发现揭示了 EXE 在肝纤维化中的新功能,并提示其在肝纤维化相关疾病中有潜在的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf12/5804406/b24c93091954/JIR2017-3072745.001.jpg

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