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Xiaochaihutang Inhibits the Activation of Hepatic Stellate Cell Line T6 Through the Nrf2 Pathway

机译:小柴胡汤通过Nrf2途径抑制肝星状细胞系T6的激活。

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摘要

Xiaochaihutang (XCHT) is one of classic prescriptions in Treatise on Febrile Diseases in China which was reported to have the effect of anti-hepatic fibrosis in vivo. Activation of hepatic stellate cells (HSCs) is now well established as a central driver of fibrosis in liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important element for anti-oxidative damage which is one of the key factors responsible for occurrence. This study was to investigate the effect of XCHT compound serum on HSCs activation and focus on the Nrf2 pathway. Rats in treatment groups were given the appropriate doses of XCHT granules (5 g/kg) and Silybin (50 mg/kg) for 6 days, and the serum were obtained. The compound serum was used to intervene HSCs. The results found that XCHT compound serum significantly inhibited the proliferation of HSCT6 cells. The number of α-SMA positive stained cells in HSCT6 cells and the content of Collagen type I (collagen-I) in supernatant were significantly decreased indicating suppression of activated HSCs. Compared with the control group, the nuclear transcription of Nrf2 and the expressions of Nqo1, GCLC, and GCLM were significantly increased in XCHT group. However, the effects of XCHT were inhibited in Nrf2-siRNA transfected HSCT6 cells. These studies demonstrated that XCHT could inhibit HSCT6 cell proliferation and activation. The mechanism might be related to up-regulation of the Nrf2 pathway against oxidative stress.
机译:小柴胡汤(XCHT)是中国《温病论》中的经典处方之一,据报道具有体内抗肝纤维化作用。肝星状细胞(HSC)的激活现已被公认是肝损伤中纤维化的主要驱动力。核因子红系2相关因子2(Nrf2)是抗氧化损伤的重要元素,而抗氧化损伤是引起发生的关键因素之一。这项研究旨在调查XCHT化合物血清对HSCs活化的影响,并重点研究Nrf2途径。给治疗组的大鼠适当剂量的XCHT颗粒(5 g / kg)和水飞蓟宾(50 mg / kg),持续6天,获得血清。复合血清用于干预HSC。结果发现,XCHT复方血清能明显抑制HSCT6细胞的增殖。 HSCT6细胞中α-SMA阳性染色细胞的数量和上清液中I型胶原(胶原I)的含量均显着降低,表明活化的HSC受到抑制。 XCHT组与对照组相比,Nrf2的核转录以及Nqo1,GCLC和GCLM的表达明显增加。但是,XCHT的作用在Nrf2-siRNA转染的HSCT6细胞中被抑制。这些研究表明,XCHT可以抑制HSCT6细胞的增殖和活化。该机制可能与抗氧化应激的Nrf2途径的上调有关。

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