Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.
Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.
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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
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发表时间：
2016-03-22
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Chang H;Wang Q;Shi T;Huo K;Li C;Zhang Q;Wang G;Wang Y;Tang B;Wang W;Wang Y
丹参丸(DQP)是临床上应用最广泛的方剂之一，对冠心病有显著的保护作用。然而，到目前为止，其对脂代谢紊乱的调节作用尚未得到全面的研究。本研究旨在探讨大鼠冠状动脉粥样硬化性心脏病模型中过氧化体增殖物激活受体α(PPARα)、脂质摄取-转运-代谢通路以及花生四烯酸(AA)介导的炎症通路的影响。将80只SD大鼠随机分为假手术组、模型组、阳性对照组和DQP组。除假手术组外，其余各组均结扎左室前降支建立冠心病模型，并给予高脂饲料喂养。假手术组仅行开胸手术。术后阳性对照组和DQP组分别给予普伐他汀和DQP每日治疗。术后28d处死大鼠，血浆生化检测血脂。用Western印迹和聚合酶链式反应检测PPARα、脂质代谢相关蛋白和AA信号通路的表达。术后28天，CHD模型大鼠出现血脂异常，表现为血脂水平升高。与假手术组比较，模型组大鼠心脏组织载脂蛋白A-I(ApoA-I)、分化簇36(CD36)和脂肪酸结合蛋白(FABP)表达下调。肉碱棕榈酰转移酶I(CPT-1A)和脂蛋白脂酶(LPL)的表达也显著降低。此外，磷脂酶A2(PLA2)和环氧合酶2(COX-2)水平上调。核因子-κB(NF-κB)和信号转导与转录激活子3(STAT3)的表达也增加。此外，模型组PPARα表达减少。DQP显著上调ApoA-I和FABP的表达，上调CPT-1A和CD36的表达。此外，大青丸还下调炎症途径中磷脂酶A_2、环氧合酶-2和核因子-κB的表达。DQP治疗不影响STAT3和LPL水平。DQP显著上调PPARα水平。DQP能有效调节CHD模型大鼠的脂质摄取-转运-代谢过程，其作用机制主要是通过激活ApoA-I-CD36-CPT-1A分子实现的。DQP能显著上调PPARα的表达。其抗炎作用部分是通过抑制磷脂酶A_2-COX_2-核因子-κB途径的表达而实现的。
Danqi pill (DQP) is one of the most widely prescribed formulas and has been shown to have remarkable protective effect on coronary heart disease (CHD). However, its regulatory effects on lipid metabolism disorders haven’t been comprehensively studied so far. We aimed to explore the effects of DQP on Peroxisome Proliferator activated receptors α (PPARα), lipid uptake-transportation-metabolism pathway and arachidonic acid (AA)-mediated inflammation pathway in rats with CHD. 80 Sprague-Dawley (SD) Rats were randomly divided into sham group, model group, positive control group and DQP group. Rat model of CHD was induced by ligation of left ventricle anterior descending artery and fed with high fat diet in all but the sham group. Rats in sham group only underwent thoracotomy. After surgery, rats in the positive control and DQP group received daily treatments of pravastatin and DQP respectively. At 28 days after surgery, rats were sacrificed and plasma lipids were evaluated by plasma biochemical detection. Western blot and PCR were applied to evaluate the expressions of PPARα, proteins involved in lipid metabolism and AA pathways. Twenty eight days after surgery, dyslipidemia developed in CHD model rats, as illustrated by elevated plasma lipid levels. Expressions of apolipoprotein A-I (ApoA-I), cluster of differentiation 36 (CD36) and fatty acid binding protein (FABP) in the heart tissues of model group were down-regulated compared with those in sham group. Expressions of carnitine palmitoyl transferase I (CPT-1A) and lipoproteinlipase (LPL) were also reduced significantly. In addition, levels of phospholipase A2 (PLA2) and cyclooxygenase 2 (COX-2) were up-regulated. Expressions of Nuclear factor-κB (NF- κB) and signal transducer and activator of transcription 3 (STAT3) also increased. Furthermore, Expression of PPARα decreased in the model group. DQP significantly up-regulated expressions of ApoA-I and FABP, as well as the expressions of CPT-1A and CD36. In addition, DQP down-regulated expressions of PLA2, COX-2 and NF-κB in inflammation pathway. Levels of STAT3 and LPL were not affected by DQP treatment. In particular, DQP up-regulated PPARα level significantly. DQP could effectively regulate lipid uptake-transportation-metabolism process in CHD model rats, and the effect is achieved mainly by activating ApoA-I-CD36-CPT-1A molecules. Interestingly, DQP can up-regulate expression of PPARα significantly. The anti-inflammatory effect of DQP is partly exerted by inhibiting expressions of PLA2-COX2 -NF-κB pathway.