Li Zhen, Wei Wei, Chen Bohong, Cai Gaotai, Li Xin, Wang Ping, Tang Jinping, Dong Wenqi
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong Province 510515, P.R. China.
Sci Rep. 2016 Mar 23;6:23508. doi: 10.1038/srep23508.
This study aims to investigate whether the use of recombinant human cytoglobin (rhCygb) impact on hepatic fibrogenesis caused by CCl4. SD (n = 150) rats were randomly divided into three groups of normal, CCl4 model and rhCygb groups. After model establishment, rats in rhCygb groups were administered daily with rhCygb (2 mg/kg, s.c.). Histological lesions were staged according to metavir. Serum parameters including ALT, AST, HA, LN, Col III and Col IV were determined. The liver proteins were separated by 2-DE and identified. As a result, the stage of hepatic damage and liver fibrosis in rhCygb groups were significantly milder than that in CCl4 model groups. Meanwhile, rhCygb dramatically reversed serum levels of ALT and AST, and also markedly decreased the liver fibrosis markers levels of LN, HA, Col III and Col IV. In 2-DE, 33 proteins among three groups with the same changing tendency in normal and rhCygb treated groups compared with CCl4 model group were identified. GO analysis showed that several identified proteins involved in oxidative stress pathway. The study provides new insights and data for administration of rhCygb reversing CCl4-induced liver fibrosis suggesting that rhCygb might be used in the treatment of liver fibrosis.
本研究旨在探讨重组人细胞红蛋白(rhCygb)的使用是否会影响由四氯化碳(CCl4)引起的肝纤维化。将150只SD大鼠随机分为正常组、CCl4模型组和rhCygb组。造模后,rhCygb组大鼠每天皮下注射rhCygb(2mg/kg)。根据梅塔维(Metavir)方法对组织学损伤进行分期。测定血清参数,包括谷丙转氨酶(ALT)、谷草转氨酶(AST)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型胶原(Col III)和Ⅳ型胶原(Col IV)。通过双向电泳(2-DE)分离并鉴定肝脏蛋白。结果显示,rhCygb组的肝损伤和肝纤维化程度明显轻于CCl4模型组。同时,rhCygb显著逆转了ALT和AST的血清水平,还明显降低了LN、HA、Col III和Col IV的肝纤维化标志物水平。在双向电泳中,鉴定出正常组和rhCygb处理组与CCl4模型组相比具有相同变化趋势的三组中的33种蛋白质。基因本体(GO)分析表明,几种鉴定出的蛋白质参与氧化应激途径。该研究为rhCygb逆转CCl4诱导的肝纤维化给药提供了新的见解和数据,表明rhCygb可能用于治疗肝纤维化。