二陈汤通过调控p38MAPK信号通路降低血脂异常痰浊阻遏证小鼠氧化应激水平的效应研究  

Effect of Erchen Decoction(二陈汤)on Reducing Oxidative Stress Levels in Mice with Dyslipidemia Phlegm-dampness Retention Syndrome by Regulating the p38 MAPK Signaling Pathway

作　　者：张晓栋 薛晓琳[1] 叶超[2] 赵久丽 杨正[3] 李鹏洋[2] 张珊 陈鹏宇 陈婧 ZHANG Xiaodong;XUE Xiaolin;YE Chao;ZHAO Jiuli;YANG Zheng;LI Pengyang;ZHANG Shan;CHEN Pengyu;CHEN Jing(Beijing University of Chinese Medicine,Beijing 102401,China;Dongzhimen Hospital Beijing University of Chinese Medicine,Beijing 100700,China;National Institute of TCM Constitution and Preventive Medicine,Beijing 100700,China;Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京102401 [2]北京中医药大学东直门医院,北京100700 [3]北京中医药大学国家中医体质与治未病研究院,北京100700 [4]北京中医药大学第三附属医院,北京100029

出　　处：《辽宁中医药大学学报》2024年第4期38-42,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82004237)。

摘　　要：目的探讨二陈汤通过调控p38MAPK信号通路降低血脂异常痰浊阻遏证小鼠氧化应激水平的效应,基于“方证相应”,研究该病-证的证候特点。方法将C57BL/6J小鼠5只设为正常组,ApoE基因敲除小鼠20只,应用多因素复合建模的方法构建血脂异常痰浊阻遏证模型,设为模型组、二陈汤低剂量治疗组、二陈汤中剂量治疗组、二陈汤高剂量治疗组。采用生化法检测血清MDA浓度水平,实时荧光定量PCR法检测主动脉内皮ICAM、E-Selectin基因转录水平,蛋白免疫印迹法检测主动脉内皮p38、p-p38蛋白表达水平。结果①与正常组相比,模型组小鼠血清MDA浓度水平、ICAM、E-Selectin基因转录水平、p-p38蛋白表达水平显著升高(P<0.05);②与模型组相比,二陈汤中、高剂量治疗组血清MDA浓度水平、ICAM、E-Selectin基因转录水平、p-p38蛋白表达水平降低(P<0.05);③与二陈汤低剂量治疗组相比,二陈汤中剂量治疗组小鼠主动脉内皮p-p38蛋白表达水平明显下降(P<0.05),二陈汤高剂量治疗组小鼠血清MDA浓度水平、E-Selectin基因转录水平明显下降(P<0.05);④与二陈汤中剂量治疗组相比,二陈汤高剂量治疗组小鼠主动脉内皮ICAM基因转录水平明显下降(P<0.05)。结论二陈汤可改善血脂异常痰浊阻遏证ICAM、E-Selectin基因转录水平,降低氧化应激程度,进而发挥对于血管内皮的保护作用,该作用的发挥机制可能与下调p38MAPK信号通路激活水平有关。方证相应,氧化应激水平增强所致的血管内皮损伤,可能是血脂异常痰浊阻遏的证候特点之一。Objective To explore the effect of Erchen Decoction(二陈汤)on reducing the level of oxidative stress in dyslipidemia phlegm-dampness retention syndrome mice by regulating the p38 MAPK signaling pathway,based on the“corresponding formula and syndrome”,and study the syndrome characteristics of this disease-syndrome.Methods The model in our experiment adopted 20 ApoE-/-and 5 C57BL/6 J mice.A normal(Nor)group consisted of the C57BL/6 J mice,while a model(Mod)group consisted of the ApoE-/-mice.After successful modeling,20 ApoE-/-mice were randomly assigned to the following groups:Mod(n=5),low-dose Erchen Decoction group(L-ECD)(n=5),medium-dose Erchen Decoction group(M-ECD)(n=5)and high-dose Erchen Decoction group(H-ECD)(n=5)group.Biochemical methods were used to detect serum MDA concentration levels.Real-time fluorescence quantitative PCR was used to detect the transcription levels of ICAM and E-Selectin genes in the aortic endothelium.And protein immunoblotting was used to detect the expression levels of p38 and p-p38 proteins in the aortic endothelium.Results①Compared with the Nor group,the serum MDA concentration level,ICAM,E-Selectin gene transcription level,and p-p38 protein expression level of the Mod group mice were significantly increased(P<0.05).②Compared with the Mod group,the serum MDA concentration level,ICAM,E-Selectin gene transcription level,and p-p38 protein expression level in the M-ECD and H-ECD groups were reduced(P<0.05).③Compared with the L-ECD group,the expression level of p-p38 protein in the aortic endothelium of mice in the M-ECD group was significantly reduced(P<0.05),while the serum MDA concentration and E-Selectin gene transcription level of mice in the H-ECD group were significantly reduced(P<0.05).④Compared with the M-ECD group,the H-ECD group showed a significant decrease in the transcription level of ICAM gene in the aortic endothelium of mice(P<0.05).Conclusion Erchen Decoction can improve the transcriptional levels of ICAM and E-Selectin genes in dyslipidemia phlegmdamp

关 键 词：二陈汤 血脂异常 痰浊阻遏证 P38MAPK信号通路 氧化应激 

分 类 号：R285.5[医药卫生—中药学]