摘要
目的:探究四妙勇安汤对动脉粥样硬化(AS)小鼠AMPK/ULK1自噬轴及炎症反应的影响。方法:将ApoE^(-/-)小鼠随机分为正常组,模型组,四妙勇安汤低、中、高剂量组,辛伐他汀组,每组10只。通过高脂饮食诱导小鼠AS模型,四妙勇安汤低(10.13 g/kg)、中(20.25 g/kg)、高(40.5 g/kg)剂量,辛伐他汀片(3 mg/kg)灌胃6周。给药结束后,收集小鼠血清和主动脉组织,全自动生化分析仪检测血清血脂水平;HE染色观察主动脉组织病理变化;透射电镜观察斑块组织自噬水平;ELISA检测血清中炎症因子IL-18、IFN-γ、CRP水平;qRT-PCR检测AMPK、ULK1、p62 mRNA表达水平;免疫荧光标记检测LC3Ⅱ、p-ULK1蛋白表达;免疫组化检测p-AMPK、p62表达。结果:与模型组比较,四妙勇安汤各剂量组及辛伐他汀组小鼠主动脉斑块明显减少,血清TC、TG、LDL-C、IFN-γ、IL-18、CRP水平均降低(P<0.05或P<0.01),HDL-C水平升高(P<0.05或P<0.01);电镜显示自噬小体增加;诱导了自噬相关因子LC3Ⅱ、AMPK、ULK1表达,抑制了p62表达。结论:四妙勇安汤可诱导AS小鼠AMPK/ULK1自噬轴,以及抑制IFN-γ、IL-18、CRP的过表达,这可能是四妙勇安汤抗AS的重要作用机制之一。
Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE^(-/-)mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γand CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱand p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemistry.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.
作者
于红红
李芳
罗瑞熙
俞琦
杨韵琪
岳文鹏
田维毅
YU Honghong;LI Fang;LUO Ruixi;YU Qi;YANG Yunqi;YUE Wenpeng;TIAN Weiyi(Institute of Traditional Chinese Medicine and Ethnic Medicine Resources,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《中国免疫学杂志》
北大核心
2025年第5期1129-1134,共6页
Chinese Journal of Immunology
基金
国家自然科学基金资助项目(81860779)
贵州省科技厅项目(黔科合基础ZK[2021]549)
贵州省中医药管理局项目(QZYY-2022-024)
贵州中医药大学研究生教育创新计划项目(YCXKYB2023012)。
作者简介
于红红,女,在读博士,高级实验师,硕士生导师,主要从事动脉粥样硬化性疾病研究,E-mail:731319210@qq.com;通信作者:田维毅,男,博士,教授,博士生导师,主要从事中西医结合基础研究,E-mail:tianweiyi1972@sina.com。
