The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway.

The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway.
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中药通过PPARγ途径影响急性心肌梗死脂糖代谢

DOI:
10.3389/fphar.2018.01209
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发表时间:
2018
影响因子:
5.6
通讯作者:
Wang Y
Wang Y
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Q;Shao M;Zhang X;Wang Q;Guo D;Yang X;Li C;Wang Y

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目的:中药丹气丸(DQP)通过调节急性心肌梗死(AMI)后心力衰竭(HF)患者的心能代谢,改善心功能。本研究旨在探讨DQP在体内和体外是否与PPARγ(过氧化物酶体增殖物激活受体γ)途径介导的脂质和糖代谢有关。材料与方法:采用Sprague-Dawley (SD)大鼠AMI后左前降支结扎法建立心衰模型。治疗28天后,采用苏木精-伊红(HE)染色观察心肌细胞形态学变化。采用高效液相色谱法测定心脏中磷酸腺苷的含量。采用正电子发射断层扫描和计算机断层扫描(PET-CT)评估心脏糖代谢。Western blotting (WB)和免疫组化(IHC)检测关键分子PPARγ、甾醇载体蛋白2 (SCP2)和长链酰基辅酶a脱氢酶(ACADL)的表达。采用氧葡萄糖剥夺-再灌注(OGD/R)诱导H9C2损伤心肌细胞模型进行体外潜在机制研究。结果:DQP治疗可使心脏免于结构、功能损伤和炎症浸润。DQP组三磷酸腺苷(ATP)和能量电荷(EC)水平也较模型组上调。进一步的结果表明,与假手术组相比,模型组的脂质代谢和糖代谢的关键酶都有所降低。有趣的是,DQP可以上调脂质代谢关键酶ACADL和SCP2,同时对糖酵解分子有促进作用。结果表明,DQP可显著提高PPARγ的表达。体外研究表明,DQP的作用可被选择性PPARγ抑制剂T0070907阻断。结论:DQP通过调节脂糖代谢,改善心功能和能量代谢,具有心脏保护作用。其作用可能通过PPARγ途径介导。
Aim: Danqi Pill (DQP), a Chinese medicine frequently prescribed in China, has been approved to improve cardiac function by regulating cardiac energy metabolism in heart failure (HF) after acute myocardial infarction (AMI) patients. The aim of this study was to explore whether the mechanism of DQP is associated to the lipid and glucose metabolism mediated via PPARγ (peroxisome proliferator-activated receptor gamma) pathway both in vivo and in vitro. Materials and Methods: Model of HF after AMI was established with ligation of left anterior descending artery on Sprague-Dawley (SD) rats. Twenty-eight days after treatment, hematoxylin–eosin (HE) staining was applied to visualize cardiomyocyte morphological changes. High performance liquid chromatography (HPLC) was performed to assess the contents of adenosine phosphates in heart. Positron emission tomography and computed tomography (PET-CT) was conducted to evaluate the cardiac glucose metabolism. Expressions of key molecules such as PPARγ, sterol carrier protein 2 (SCP2) and long chain acyl CoA dehydrogenase (ACADL) were measured by Western blotting (WB) and immunohistochemistry (IHC). Oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro. Results: Treatment with DQP rescued hearts from structural and functional damages as well as inflammatory infiltration. Levels of adenosine triphosphate (ATP) and energy charge (EC) in DQP group were also up-regulated compared to model group. Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compromised in model group compared to sham group. Intriguingly, DQP could up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously. Results on upstreaming signaling pathway demonstrated that DQP could dramatically increase the expressions of PPARγ. In vitro study suggested the efficacy of DQP could be blocked by T0070907, a selective PPARγ inhibitor. Conclusion: DQP has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism. The effects may be mediated by PPARγ pathway.
DOI: 10.1007/978-3-319-55330-6_4
发表时间: 2017-01-01
期刊: MITOCHONDRIAL DYNAMICS IN CARDIOVASCULAR MEDICINE
影响因子: --
作者:
Sheeran, Freya L.;Pepe, Salvatore
通讯作者: Pepe, Salvatore
丹芪丸对冠心病模型大鼠PPARα、血脂紊乱及花生四烯酸通路的影响
DOI: 10.1186/s12906-016-1083-3
发表时间: 2016-03-22
影响因子: --
作者:
Chang H;Wang Q;Shi T;Huo K;Li C;Zhang Q;Wang G;Wang Y;Tang B;Wang W;Wang Y
通讯作者: Wang Y
DOI: 10.1016/j.cbi.2018.02.011
发表时间: 2018-03-25
影响因子: 5.1
作者:
Muthukumaran, Padmanaban;Thiyagarajan, Gopal;Lakshmi, Baddireddi Subhadra
通讯作者: Lakshmi, Baddireddi Subhadra
DOI: 10.1177/1536012117704767
发表时间: 2017-01-01
期刊: Molecular imaging
影响因子: 2.8
作者:
Choi H;Han JH;Lim SY;Lee I;Cho YS;Chun EJ;Lee WW
通讯作者: Lee WW
DOI: 10.1016/j.bcp.2013.04.022
发表时间: 2013-07-15
影响因子: 5.8
作者:
Takahashi-Yanaga, Fumi
通讯作者: Takahashi-Yanaga, Fumi