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八宝丹通过TLR4信号通路抑制肝星状细胞的激活和增殖来减轻肝纤维化。

Babao Dan attenuates hepatic fibrosis by inhibiting hepatic stellate cells activation and proliferation via TLR4 signaling pathway.

作者信息

Liang Lei, Yang Xue, Yu Yang, Li Xiaoyong, Wu Yechen, Shi Rongyu, Jiang Jinghua, Gao Lu, Ye Fei, Zhao Qiudong, Li Rong, Wei Lixin, Han Zhipeng

机构信息

Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.

Medical College of Soochow University, Suzhou, China.

出版信息

Oncotarget. 2016 Dec 13;7(50):82554-82566. doi: 10.18632/oncotarget.12783.

Abstract

Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers. Meanwhile, BBD attenuated hepatic inflammation and fibrosis in DEN-induced rat livers through histopathological examination and hepatic hydroxyproline content. Furthermore, we found that BBD inhibited hepatic stellate cells activation and proliferation without altering the concentration of lipopolysaccharide (LPS) in portal vein. In vitro study, serum from BBD treated rats (BBD-serum) could also significantly suppress LPS-induced HSCs activation through TLR4/NF-κB pathway. In addition, BBD-serum also inhibited the proliferation of HSCs by regulating TLR4/ERK pathway. Our study demonstrated that BBD may provide a new therapy strategy of hepatic injury and hepatic fibrosis.

摘要

八宝丹(BBD)是一种中药,已被广泛用作治疗慢性肝病的补充和替代药物。在本研究中,我们旨在观察八宝丹对二乙基亚硝胺(DEN)诱导的大鼠肝纤维化的保护作用,并探讨其可能的机制。在给予DEN的同时给予八宝丹。八周后,血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的值表明,八宝丹能显著保护肝脏免受DEN的损伤,且对正常大鼠肝脏无明显副作用。同时,通过组织病理学检查和肝脏羟脯氨酸含量测定,八宝丹减轻了DEN诱导的大鼠肝脏炎症和纤维化。此外,我们发现八宝丹抑制肝星状细胞的激活和增殖,而不改变门静脉中脂多糖(LPS)的浓度。体外研究表明,八宝丹处理大鼠的血清(BBD-血清)也能通过TLR4/NF-κB途径显著抑制LPS诱导的肝星状细胞激活。此外,BBD-血清还通过调节TLR4/ERK途径抑制肝星状细胞的增殖。我们的研究表明,八宝丹可能为肝损伤和肝纤维化提供一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a238/5347713/096017c5fa97/oncotarget-07-82554-g001.jpg

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