西藏胡黄连醇提物对动脉粥样硬化小鼠主动脉PPARγ和PON1表达的影响
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摘要
目的观察西藏胡黄连醇提物(ethanol extraction of Picrorhiza scrophulariiflora,EPS)对apoE~(-/-)小鼠动脉粥样硬化的干预机制。方法将30只apoE~(-/-)小鼠随机分为对照组,模型组,EPS低、中、高剂量组和辛伐他汀组,每组5只。分别给予相应药物灌胃,对照组和模型组给予等体积的蒸馏水,连续灌胃12周。超声和病理切片观察各组主动脉中的斑块形成情况,试剂盒检测血清生化指标,蛋白免疫印迹法和实时荧光定量聚合酶链式反应检测PPARγ和PON1的表达。结果与模型组比较,EPS和辛伐他汀组可以显著减少动脉粥样硬化斑块的形成,降低血清TC,LDL-C,TNF-α,IL-6,MCP-1,MDA水平(P<0.05,P<0.01,P<0.001),显著升高GSH-Px,SOD活性(P<0.01,P<0.001),增加主动脉中PPARγ和PON1的表达显(P<0.001)。结论西藏胡黄连具有改善动脉粥样硬化的功能,其机制可能与上调动脉壁中PPARγ和PON1的表达有关。
Objective To observe the effect mechanism of ethanol extraction of Picrorhiza scrophulariiflora(EPS) on atherosclerosis(AS) in apoE~(-/-) mice. Methods Thrity apoE~(-/-) mice were randomly divided into control group, model group, EPS low, medium, high dose group and simvastatin group, five apoE~(-/-) mice in each group. The corresponding drugs were given by gavage. The control group and model group were given an equal volume of distilled water for 12 weeks. After 12 weeks of administration, echocardiography and Oil red O staining were used to detect the plaque formation in the aorta. The kits were used to detect serum biochemical indicators. Western blot and RT-PCR were used to detect the expressions of PPARγ and PON1.Results Compared with the model group, EPS low, medium, high dose group and simvastatin group could significantly reduced the formation of atherosclerotic plaques, reduced the levels of serum TC, LDL-C, TNF-α, IL-6, MCP-1 and MDA(P<0.05, P<0.01, P<0.001), increased the activity of SOD and GSH-Px(P<0.05, P<0.01), and increased the expression of PPARγ and PON1 in aorta(P<0.001). Conclusion Picrorhiza scrophulariiflora has the function of improving atherosclerosis, and the mechanism may be related to up-regulating the gene expression of PPARγ and PON1.
Objective To observe the effect mechanism of ethanol extraction of Picrorhiza scrophulariiflora(EPS) on atherosclerosis(AS) in apoE~(-/-) mice. Methods Thrity apoE~(-/-) mice were randomly divided into control group, model group, EPS low, medium, high dose group and simvastatin group, five apoE~(-/-) mice in each group. The corresponding drugs were given by gavage. The control group and model group were given an equal volume of distilled water for 12 weeks. After 12 weeks of administration, echocardiography and Oil red O staining were used to detect the plaque formation in the aorta. The kits were used to detect serum biochemical indicators. Western blot and RT-PCR were used to detect the expressions of PPARγ and PON1.Results Compared with the model group, EPS low, medium, high dose group and simvastatin group could significantly reduced the formation of atherosclerotic plaques, reduced the levels of serum TC, LDL-C, TNF-α, IL-6, MCP-1 and MDA(P<0.05, P<0.01, P<0.001), increased the activity of SOD and GSH-Px(P<0.05, P<0.01), and increased the expression of PPARγ and PON1 in aorta(P<0.001). Conclusion Picrorhiza scrophulariiflora has the function of improving atherosclerosis, and the mechanism may be related to up-regulating the gene expression of PPARγ and PON1.
引文
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[2] 罗俊,王淑珍.颈动脉粥样硬化与心血管疾病的关系[J].心血管病学进展,2011,32(2):236.
[3] 李薇,杜军保.动脉粥样硬化发病机制研究进展[J].中华实用儿科临床杂志,2009,24(1):58.
[4] Castrillo A,Tontonoz P.PPARs in atherosclerosis:the clot thickens[J].J Clin Invest,2004,114(11):1538.
[5] 赵水平,李毅夫,彭道泉,等.急性冠脉综合征单核细胞过氧化物酶体增生激活型受体γ基因表达及其与细胞黏附分子相关性研究[J].中华心血管病杂志,2001,29(10):580.
[6] Bruemmer D,Blaschke F,Law R E.New targets for PPARgamma in the vessel wall:implications for restenosis[J].Int J Obes,2005,29 Suppl 1(Suppl 1):S26.
[7] Mackness M,Mackness B.Targeting paraoxonase-1 in atherosclerosis[J].Expert Opin Ther Targets,2013,17(7):829.
[8] Aviram M,Rosenblat M.Paraoxonases 1,2,and 3,oxidative stress,and macrophage foam cell formation during atherosclerosis development[J].Free Radic Biol Med,2004,37(9):1304.
[9] 黄林清,张恩娟,王军.胡黄连的研究进展[J].中国药业,2007,16(7):1.
[10] 国家药典委员会.中国药典,一部[S].北京:中国医药科技出版社,2015:242.
[11] Zhi J G,Fan F H,Shang X L,et al.Picrorhiza scrophulariiflora,improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation[J].Int J Cardiol,2009,136(3):315.
[12] Liuzzo G.Ross R.Atherosclerosis-An inflammatory disease[J].N Engl J Med,1999,26(4):221.
[13] Satoh N,Ogawa Y,Usui T,et al.Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect[J].Diabetes Care,2003,26(9):2493.
[14] Ishibashi S,Ishibashi S,Ishibashi S.PPAR gamma and atherosclerosis[J].Jpn J Pharmacol,2002,88:25P.
[15] 张春侠.超声检测对颈动脉粥样硬化颈动脉阻力指数(RI)的分析研究[J].医药前沿,2014,(36):129.
[16] 李蕊,马历历,方婧.经颅多普勒搏动指数(PI)与脑血管病危险因素的临床分析[J].中国社区医师(医学专业),2010,12(32):134.
[17] 张恩伟.血脂水平与冠心病患者动脉粥样硬化的关系研究[J].中国药物经济学,2013,(2):224.
[18] 张安邦,高杰,李令根,等.相关炎症因子与动脉粥样硬化的关系[J].中国中西医结合外科杂志,2014,20(5):563.
[19] Asha K,Singal A,Sharma S B,et al.Dyslipidaemia & oxidative stress in patients of psoriasis:Emerging cardiovascular risk factors[J].Indian J Med Res,2017,146(6):708.
[20] Kurabayashi M.Atherosclerosis and Oxidative Stress[J].Jpn J Apheresis,2008,27(3):22.