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

The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway.
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中药及其有效成分通过PPARs-PGC1α通路对冠心病的作用

DOI:
10.1186/s12906-016-1496-z
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发表时间:
2016-12-12
影响因子:
--
通讯作者:
Wang W
Wang W
中科院分区:
医学3区
文献类型:
--
作者:
Wang Q;Li C;Zhang Q;Wang Y;Shi T;Lu L;Zhang Y;Wang Y;Wang W

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丹芪丸在我国处方广泛,对冠心病有明确的心脏保护作用。本课题组前期研究证明DQP能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,DQP及其主要成分丹参总酸和三七总皂苷(DS)对脂代谢紊乱的调节机制至今尚未得到全面的研究。采用结扎左前降支(LAD)的方法建立大鼠冠心病模型。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脏功能。采用逆转录聚合酶链反应或蛋白质印迹法检测细胞能量代谢途径中转录因子和关键分子的表达。在缺血心脏模型中,心功能受到严重损害,但DQP和DS治疗后心功能得到改善。模型组LPL表达下调。DQP和DS均能上调LPL mRNA的表达。缺血心肌组织中参与脂质转运和摄取的膜蛋白如FABP 4和CPT-1A表达下调。DQP和DS处理通过上调FABP 4和CPT-1A的表达来调节脂质代谢。DQP和DS也抑制细胞色素P450的表达。缺血模型组转录因子PPARα、PPARγ、RXRA和PGC-1α表达下调。DQP和DS可上调这些因子的表达。然而,DS对PPARs共激活剂PGC-1α的作用优于DQP。DQP和DS同时对AKT 1/2、ERK和PI 3 K等信号通路中的关键分子进行调控。丹参酮酸和三七是丹芪丸改善缺血性心脏模型脂质代谢的主要有效成分。这种作用可能是通过调节转录因子如PPARs、RXRA和PGC-1α介导的。
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. 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. 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. 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.
DOI: 10.1161/01.cir.0000441139.02102.80
发表时间: 2014-01-21
期刊: Circulation
影响因子: 37.8
作者:
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者: American Heart Association Statistics Committee and Stroke Statistics Subcommittee
salvianolic酸:具有多种心血管保护机制的小型化合物。
DOI: 10.1186/1423-0127-18-30
发表时间: 2011-05-11
影响因子: 11
作者:
Ho JH;Hong CY
通讯作者: Hong CY
DOI: 10.1161/hc3901.096665
发表时间: 2001-10-02
期刊: CIRCULATION
影响因子: 37.8
作者:
LaRosa, JC
通讯作者: LaRosa, JC
DOI: 10.1155/2008/253817
发表时间: 2008
期刊: PPAR research
影响因子: 2.9
作者:
Duncan JG;Finck BN
通讯作者: Finck BN
DOI: 10.1007/s00424-007-0321-4
发表时间: 2008-01-01
影响因子: 4.5
作者:
Hu, Yeshi;Chen, Xin;Bian, Jin-Song
通讯作者: Bian, Jin-Song