红花提取物通过调节PI3K/Akt/FoxO信号通路改善酒精性肝病  

Carthamus tinctorius L. extract ameliorates alcoholic liver disease by modulating PI3K/Akt/FoxO signaling pathway

作　　者：王文萱 付向磊 戚曼 范芙蓉 朱芙蓉 王元创 张凯月 刘敏 楚生辉 WANG Wen-xuan;FU Xiang-lei;QI Man;FAN Fu-rong;ZHU Fu-rong;WANG Yuan-chuang;ZHANG Kai-yue;LIU Min;CHU Sheng-hui(Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,Ministry of Education,School of Pharmacy,Shihezi University,Shihezi Xinjiang 832000,China)

机构地区：[1]石河子大学药学院,新疆植物药资源利用教育部重点实验室,新疆石河子832000

出　　处：《中国药理学通报》2024年第6期1137-1145,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学地区基金资助项目(No 82160121)。

摘　　要：目的探讨红花提取物(Carthamus tinctorius L.extract,CTLE)对酒精诱导的肝损伤小鼠氧化应激、脂质代谢和凋亡水平的影响及其作用机制。方法采用慢性酒精喂养加急性酒精灌胃的酒精性肝病小鼠模型造模。小鼠被随机分为4组,造模期间每天观察小鼠状态变化并记录体质量。造模结束后,收集各组小鼠血液和肝脏组织。对小鼠血液进行生化分析。HE染色和油红O染色进一步评价小鼠肝脏病理损伤程度。应用实时荧光定量PCR(quantitative real-time PCR,qPCR)和Western blot法检测p-PI3K、PI3K、p-Akt、Akt、p-mTOR、mTOR、p-FoxO1、FoxO1、p-FoxO3a、FoxO3a、p-FoxO4、FoxO4、BCL-2和BAX因子的mRNA和蛋白表达水平。结果与模型组相比,CTLE给药组小鼠肝脏病理损伤程度和脂质沉积有所改善;小鼠血清及肝脏中的生化相关指标,如ALT、AST、TG、TC、MDA水平有所降低,GSH、SOD水平有所升高。并且通过调控PI3K/Akt/FoxO通路产生了更多的SOD,减少了活性氧(reactive oxygen species,ROS)对机体的损伤和细胞凋亡。结论CTLE可以通过PI3K/Akt/FoxO通路发挥抗氧化应激和抗凋亡作用,减轻小鼠的酒精性肝损伤,为治疗酒精性肝病和开发相关药物提供新的思路。Aim To investigate the effects of Carthamus tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with alcohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic pathological injury and reduced lipid deposition.The biochemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the development of related drugs.

关 键 词：红花提取物 酒精性肝病 脂质代谢 氧化应激 细胞凋亡 PI3K/Akt/FoxO信号通路 

分 类 号：R-332[医药卫生] R284.1R329.25R349.1R575