益气通脉方对ApoE-/-小鼠动脉粥样硬化的影响及机制
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篇名: 益气通脉方对ApoE-/-小鼠动脉粥样硬化的影响及机制
TITLE: Effects of Yiqi tongmai formula on atherosclerosis in ApoE-/- mice and its mechanism
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,2.6mg/(kg·d)]和益气通脉方低、中、高剂量组[0.46、0.91、1.82g/(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。
ABSTRACT: 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 12 consecutive 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-1β and 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 mTOR 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 metabolism, reduce inflammatory response, and delay plaque development in AS mice. Its effect may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.
期刊: 2024年第35卷第18期
作者: 任权娜;陈雨晗;汪坤;马鸣;杨艳华;张雨;赵旭
AUTHORS: REN Quanna,CHEN Yuhan,WANG Kun,MA Ming,YANG Yanhua,ZHANG Yu,ZHAO Xu
关键字: 益气通脉方;动脉粥样硬化;炎症反应;PI3K/Akt/mTOR信号通路
KEYWORDS: Yiqi tongmai formula; atherosclerosis; inflammation response; PI3K/Akt/mTOR signaling pathway
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