摘要
目的:基于Keap1/Nrf2/HIF-1α信号通路探讨降脂颗粒对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)小鼠的影响。方法:24只雄性C57BL/6J小鼠随机分为对照组、模型组以及降脂颗粒低、高剂量(120、240 mg/kg)组。高脂饮食诱导8周后,分别灌胃给药。降脂颗粒治疗8周后,检测小鼠外周血肝功能指标和血脂水平;HE和油红O染色观察肝组织病理学改变;RT-PCR检测肝组织炎症因子和Keap1、Nrf2、Hif1a及其通路下游相关基因的mRNA表达水平;Western Blot及免疫荧光染色检测肝组织Keap1、Nrf2、HIF-1α蛋白表达水平和定位。结果:与模型组比较,降脂颗粒高剂量组显著下调小鼠肝脏TG水平(P<0.01),抑制Keap1、Hif1a mRNA水平(P<0.01)及HIF-1α蛋白表达(P<0.01);并促进了Nrf2下游抗氧化基因的表达,如Gclm、Nqo1 mRNA(P<0.05,P<0.01)。结论:降脂颗粒可通过调控Keap1/Nrf2/HIF-1α通路有效改善NAFLD小鼠肝脏脂肪变性和炎症。
Objective:To observe the effects of Jiangzhi Granules on high-fat diet-induced non-alcoholic fatty liver disease(NAFLD)in mice based on the Keap1/Nrf2/HIF-1α signaling pathway.Methods:Twenty-four male C57BL/6J mice were randomly divided into control group,model group,Jiangzhi Granules low-dose group,and Jiangzhi Granules high-dose group.After 8 weeks of modeling,they were administrated by intragastric administration.After 8 weeks of intervention,peripheral blood liver function indexes and blood lipid levels were detected.The histopathological changes of liver were observed by HE and oil red O staining.The mRNA expression levels of inflammatory factors,Keapl,Nrf2,Hifla,and their downstream related genes in the liver tissue were detected by RT-PCR.The protein expression levels and localization of Keapl,Nrf2 and HIF-1αin liver tissues were detected by Western Blot and immunofluorescence staining.Results:Compared with the model group,Jiangzhi Granules high-dose group significantly down-regulated mouse liver TG levels(P<0.01),inhibited Keapl and Hifla mRNA levels(P<0.01)and HIF-1α protein expression(P<0.01);and promoted the expression of antioxidant genes downstream of Nrf2,such as Gclm and Nqo1(P<0.05,P<0.01).Conclusion:Jiangzhi Granules can effectively improve hepatic steatosis and inflammation of NAFLDmiceby regulatingKeapl/Nrf2/HIF-1α pathway.
作者
马赞颂
圣炜
吴琰
张梓琪
季光
张莉
MA Zansong;SHENG Wei;WU Yan;ZHANG Ziqi;JI Guang;ZHANG Li(The Fifth People's Hospital of Shanghai,Shanghai 200240,China;Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Graduate School of Shanghai University of Traditional Chinese Medicine,Shanghai 200120,China)
出处
《中华中医药杂志》
北大核心
2025年第7期3381-3386,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.82274448)。
