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中药及其有效成分通过PPARs-PGC1α通路对冠心病的影响。

The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway.

作者信息

Wang Qiyan, Li Chun, Zhang Qian, Wang Yuanyuan, Shi Tianjiao, Lu Linghui, Zhang Yi, Wang Yong, Wang Wei

机构信息

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.

Modern Research Center for Traditional Chinese Medicine,School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.

出版信息

BMC Complement Altern Med. 2016 Dec 12;16(1):514. doi: 10.1186/s12906-016-1496-z.

Abstract

BACKGROUND

DanQi pill (DQP) is prescribed widely in China and has definite cardioprotective effect on coronary heart disease. Our previous studies proved that DQP could effectively regulate plasma levels of high density lipoprotein (HDL) and low density lipoprotein (LDL). However, the regulatory mechanisms of DQP and its major components Salvianolic acids and Panax notoginseng saponins (DS) on lipid metabolism disorders haven't been comprehensively studied so far.

METHODS

Rat model of coronary heart disease was induced by left anterior descending (LAD) artery ligation operations. Rats were divided into sham, model, DQP treated, DS treated and positive drug (clofibrate) treated groups. At 28 days after surgery, cardiac functions were assessed by echocardiography. Expressions of transcription factors and key molecules in energy metabolism pathway were measured by reverse transcriptase polymerase chain reaction or western blotting.

RESULTS

In ischemic heart model, cardiac functions were severely injured but improved by treatments of DQP and DS. Expression of LPL was down-regulated in model group. Both DQP and DS could up-regulate the mRNA expression of LPL. Membrane proteins involved in lipid transport and uptake, such as FABP4 and CPT-1A, were down-regulated in ischemic heart tissues. Treatment with DQP and DS regulated lipid metabolisms by up-regulating expressions of FABP4 and CPT-1A. DQP and DS also suppressed expression of cytochrome P450. Furthermore, transcriptional factors, such as PPARα, PPARγ, RXRA and PGC-1α, were down-regulated in ischemic model group. DQP and DS could up-regulate expressions of these factors. However, DS showed a better efficacy than DQP on PGC-1α, a coactivator of PPARs. Key molecules in signaling pathways such as AKT1/2, ERK and PI3K were also regulated by DQP and DS simultaneously.

CONCLUSIONS

Salvianolic acids and Panax notoginseng are the major effective components of DanQi pill in improving lipid metabolism in ischemic heart model. The effects may be mediated by regulating transcriptional factors such as PPARs, RXRA and PGC-1α.

摘要

背景

丹七片(DQP)在中国被广泛应用,对冠心病具有明确的心脏保护作用。我们之前的研究证明,DQP可有效调节血浆高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平。然而,迄今为止,DQP及其主要成分丹酚酸和三七总皂苷(DS)对脂质代谢紊乱的调节机制尚未得到全面研究。

方法

通过左冠状动脉前降支(LAD)结扎手术诱导大鼠冠心病模型。将大鼠分为假手术组、模型组、DQP治疗组、DS治疗组和阳性药物(氯贝丁酯)治疗组。术后28天,通过超声心动图评估心功能。通过逆转录聚合酶链反应或蛋白质免疫印迹法检测能量代谢途径中转录因子和关键分子的表达。

结果

在缺血性心脏模型中,心功能严重受损,但DQP和DS治疗可使其改善。模型组脂蛋白脂肪酶(LPL)表达下调。DQP和DS均可上调LPL的mRNA表达。缺血性心脏组织中参与脂质转运和摄取的膜蛋白,如脂肪酸结合蛋白4(FABP4)和肉碱/有机阳离子转运体1A(CPT-1A)表达下调。DQP和DS治疗通过上调FABP4和CPT-1A的表达来调节脂质代谢。DQP和DS还抑制细胞色素P450的表达。此外,转录因子,如过氧化物酶体增殖物激活受体α(PPARα)、过氧化物酶体增殖物激活受体γ(PPARγ)、视黄酸X受体α(RXRA)和过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)在缺血模型组中表达下调。DQP和DS可上调这些因子的表达。然而,在PPARs的共激活因子PGC-1α方面,DS的疗效优于DQP。信号通路中的关键分子,如蛋白激酶B1/2(AKT1/2)、细胞外信号调节激酶(ERK)和磷脂酰肌醇-3激酶(PI3K)也同时受到DQP和DS的调节。

结论

丹酚酸和三七总皂苷是丹七片改善缺血性心脏模型脂质代谢的主要有效成分。其作用可能通过调节PPARs、RXRA和PGC-1α等转录因子介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1528/5153825/4d6818fa55c7/12906_2016_1496_Fig1_HTML.jpg

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