摘要
目的探究益气通脉方对载脂蛋白E基因敲除(ApoE^(-/-))小鼠脉粥样硬化(AS)的影响及机制。方法将40只ApoE^(-/-)小鼠随机分为模型组、阳性对照组[阿托伐他汀钙,2.6 mg/(kg·d)]和益气通脉方低、中、高剂量组[0.46、0.91、1.82 g/(kg·d),以生药量计],每组8只;另取C57BL/6J小鼠8只作为正常组。除正常组外,其余各组小鼠给予高脂饲料并灌胃相应药液或生理盐水,每天1次,连续12周。末次给药后,检测小鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平及肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、单核细胞趋化蛋白1(MCP-1)含量;检测并计算各组小鼠主动脉斑块面积占比,观察主动脉窦病理形态学变化;检测小鼠主动脉中磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(又称Akt)及哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化水平。结果与模型组比较,益气通脉方中、高剂量组小鼠血清TC、TG、LDL-C水平和TNF-α、IL-1β、MCP-1(含低剂量组)含量均显著降低,高剂量组的HDL-C含量显著升高(P<0.05或P<0.01);益气通脉方各剂量组小鼠主动脉斑块均有不同程度减少,脂质沉积、炎症细胞浸润等病理改变均有不同程度减轻;益气通脉方中、高剂量组小鼠主动脉斑块面积占比和主动脉中PI3K、Akt、mTOR蛋白的磷酸化水平均显著降低(P<0.05或P<0.01)。结论益气通脉方可改善AS小鼠的脂质代谢,减轻炎症反应,延缓斑块发展,其作用可能与抑制PI3K/Akt/mTOR信号通路激活有关。
OBJECTIVE To investigate the effects of Yiqi tongmai formula on atherosclerosis(AS)in ApoE-/-mice and its mechanism.METHODS Forty ApoE-/-mice were randomly divided into model group,positive control group[atorvastatin calcium,2.6 mg/(kg·d)],and low-dose,medium-dose and high-dose groups of Yiqi tongmai formula[0.46,0.91,1.82 g/(kg·d),by raw material],with 8 mice in each group.Eight C57BL/6J mice were selected as the normal group.Except for the normal group,the other groups were given a high-lipid diet and relevant drug or normal saline intragastrically,once a day,for 12consecutive weeks.After the last medication,the serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)as well as the contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and monocyte chemoattractant protein-1(MCP-1)were measured in mice.The proportion of aortic plaque area in each group of mice was detected and calculated,and the pathological morphological changes of the aortic sinus were observed;the protein phosphorylation levels of aortic phosphoinositide 3-kinase(PI3K),protein kinase B(aka Akt)and mammalian target of rapamycin(mTOR)were examined.RESULTS Compared with the model group,the serum levels of TC,TG and LDL-C and the contents of TNF-α,IL-1βand MCP-1(including low-dose group)were decreased significantly in medium-dose and high-dose groups of Yiqi tongmai formula,while the content of HDL-C in high-dose group was increased significantly(P<0.05 or P<0.01);aortic plaques of the mice were reduced in Yiqi tongmai formula groups to different extents,and pathological changes such as lipid deposition and inflammatory cell infiltration were relieved to different extents;the proportion of aortic plaque area,the protein phosphorylation levels of PI3K,Akt and m TOR in aortic tissue were significantly reduced in medium-dose and high-dose groups of Yiqi tongmai formula(P<0.05 or P<0.01).CONCLUSIONS Yiqi tongmai formula can improve lipid metabolis
作者
任权娜
陈雨晗
汪坤
马鸣
杨艳华
张雨
赵旭
REN Quanna;CHEN Yuhan;WANG Kun;MA Ming;YANG Yanhua;ZHANG Yu;ZHAO Xu(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Dept.of Pharmacy,Henan Provincial Hospital of Traditional Chinese Medicine/the Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450002,China)
出处
《中国药房》
CAS
北大核心
2024年第18期2232-2237,共6页
China Pharmacy
基金
河南省重点研发与推广专项(科技攻关)(No.212102311114)
河南省中医药拔尖人才培养项目(No.豫卫中医函[2021]15号)
河南省中医药科学研究专项课题(No.20-21ZYZD08,No.2023ZY1015,No.2023ZY2081)。
