摘要
目的:基于Kelch样环氧氯丙烷相关蛋白1(Keap1)/核因子E2相关因子(Nrf2)/核因子κB通路研究金昭胶囊对慢性酒精性肝损伤小鼠的保护作用。方法:小鼠按体质量随机区组法分为空白组,模型组,阳性药组,金昭胶囊低、中、高剂量组,每组10只。除空白组外,其余各组小鼠每日灌胃50%乙醇10 mL/kg。各组持续给药4周后,观察小鼠状态,测定血清转氨酶活性、肝组织乙醇及脂肪代谢相关酶活性、抗氧化酶活性及Keap1/Nrf2/核因子κB通路相关指标并取肝脏进行苏木精-伊红(HE)病理学检查。结果:与模型组比较,金昭胶囊各剂量组小鼠血清转氨酶活性、肝组织乙醇及脂肪代谢相关酶活性、抗氧化酶水平、炎症介质中白细胞介素-10(IL-10)水平、Nrf2 mRNA水平及Nrf2、血红素加氧酶1(HO-1)表达水平均显著升高(P<0.05、P<0.01);肝组织炎症介质中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平、Keap1mRNA、核因子κB亚基p65亲和肽(NF-κB p65)mRNA水平及Keap1、NF-κB p65和磷酸化核因子κB抑制蛋白α(pIκ-Bα)表达均显著降低(P<0.05、P<0.01)。结论:金昭胶囊具有保护慢性酒精性肝损伤的功效,其作用机制可能与增强肝组织中乙醇代谢酶、抗氧化酶活性,调节炎症介质水平和Keap1/Nrf2/核因子κB通路各指标mRNA及蛋白表达水平相关。
Objective:To decipher the mechanism of Jinzhao Capsules in protecting mice from chronic alcoholic liver injury via the Kelch-like ECH-associated protein-1/nuclear factor erythroid 2-related factor 2/nuclear factor-κB(Keap1/Nrf2/NF-κB) pathway.Methods:Mice were randomized into blank,model,positive drug,and low-,medium-,and high-dose Jinzhao Capsules groups(n=10) according to their body weights.The mice in the other groups except the blank group were administrated with 50% ethanol at a dose of 10 mL/kg by gavage every day.After four consecutive weeks of drug administration,the status of mice was observed,and the activity of transaminase in the serum as well as the levels of ethanol,fat metabolism-related enzymes,and antioxidant enzymes in the liver were measured.In addition,the protein and mRNA levels of factors in the Keap1/Nrf2/NF-κB pathway were determined.The liver tissue was sampled and stained with hematoxylin and eosin,and the pathological changes were examined.Results:Compared with the model group,Jinzhao Capsules groups showed increased transaminase activity in the serum,elevated levels of ethanol,fat metabolism-related enzymes,antioxidant enzymes,and interleukin-10(IL-10) in the liver,up-regulated mRNA level of Nrf2 and protein levels of Nrf2 and heme oxygenase-1(P<0.05,P<0.01),lowered levels of tumor necrosis factor-α and interleukin-6,and down-regulated mRNA levels of Keap1 and NF-κB p65 and protein levels of Keap1,NF-κB p65,phospho-inhibitory subunit of NF-κB α in the liver(P<0.05,P<0.01).Conclusion:Jinzhao Capsules can protect mice from chronic alcoholic liver injury by enhancing the activities of alcohol metabolism-related enzymes and antioxidant enzymes in the liver tissue and regulating the levels of inflammatory mediators and the mRNA and protein levels of factors in the Keap1/Nrf2/NF-κB pathway.
作者
贾岚
高晶
李丽
邵紫萱
扈觐玺
刘佳琪
冯广旭
王景霞
JIA Lan;GAO Jing;LI Li;SHAO Zixuan;HU Jinxi;LIU Jiaqi;FENG Guangxu;WANG Jingxia(Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《世界中医药》
CAS
北大核心
2024年第12期1772-1778,1786,共8页
World Chinese Medicine
基金
国家自然科学基金项目(82074036)——基于调节“环核苷酸-内分泌-细胞因子网络系统”研究白芍养肝阴的物质基础与作用机制
国家中医药管理局中医药行业科研专项(201507004)——含毒性及疑似毒性药材中成药的有效性和安全性文献研究。
关键词
金昭胶囊
酒精性肝损伤
乙醇代谢
脂肪代谢
炎症介质
氧化应激
Kelch样环氧氯丙烷相关蛋白1/核因子E2相关因子/核因子κB
小鼠
Jinzhao Capsules
Alcoholic liver injury
Ethanol metabolism
Fat metabolism
Inflammatory mediators
Oxidative stress
Kelch-like ECH-associated protein-1/nuclear factor erythroid 2-related factor 2/nuclear factor-κB(Keap1/Nrf2/NF-κB)
Mice
