血管软化丸调控CD40-CD40L系统及抗动脉粥样硬化的作用机制研究
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摘要
目的:观察血管软化丸对CD40-CD40L系统血小板活化标志物的影响,研究血管软化丸抗动脉粥样硬化的作用机制。方法:40只雄性ApoE~(-/-)小鼠分为4组(模型组、氯吡格雷组、血管软化丸高剂量组、血管软化丸低剂量组),另选10只C57BL/6小鼠作为对照组。干预12周后检测血脂、外周血小板表面PAC-1、CD40L表达,观察主动脉组织病理形态学改变;检测主动脉组织CD40L表达水平。结果:与模型组相比,血管软化丸高剂量组和血管软化丸低剂量组血清血脂TC、TAG和LDL-C水平均明显降低(均P<0.05),HDL-C水平明显升高(P<0.05);血管软化丸高剂量组和血管软化丸低剂量组血动脉粥样硬化病变程度明显较模型组和氯吡格雷组轻,血管软化丸两个剂量组血小板活化标志物水平均较模型组明显降低(均P<0.05);模型组动脉组织CD40L表达光密度值明显高于正常组(P<0.05)。结论:血管软化丸抗动脉粥样硬化的作用机制可能与血管软化丸能够调节血脂,调控CD40-CD40L系统抑制血小板活化作用有关。
Objective: To observe the effect of Vascular Softening Pills on platelet activation markers of CD40-CD40 L system and study the mechanism of anti-atherosclerosis of vascular softening pills. Methods:Forty male ApoE~(-/-) mice were divided into 4 groups(model group, clopidogrel group, Vascular Softening Pills high dose group, Vascular Softening Pills low dose group), and another 10 C57 BL/6 mice were used as the control group. After 12 weeks intervention, the expressions of PAC-1 and CD40 L on blood lipids and peripheral platelets were measured and the pathological changes of aortic tissues were observed. The expression of CD40 L in aortic tissues was detected. Results:Compared with the model group, serum TC, TAG and LDL-C levels in the high dose group of Vascular Softening Pills and low dose Vascular Softening Pills group were significantly lower(P<0.05), and HDL-C levels were significantly higher(P<0.05). The degree of atherosclerotic lesions in the high dose group of Vascular Softening Pills and the low dose group of Vascular Softening Pills was significantly lower than that in the model group and clopidogrel group. The level of platelet activation markers in the two dose groups of Vascular Softening Pills was significantly higher than that in the model group. The decrease was observed(P<0.05). The optical density of CD40 L in the model group was significantly higher than that in the normal group(P<0.05). Conclusion:The mechanism of anti-atherosclerosis of Vascular Softening Pills may be related to regulating blood lipids and regulating the inhibition of platelet activation by CD40-CD40 L system.
Objective: To observe the effect of Vascular Softening Pills on platelet activation markers of CD40-CD40 L system and study the mechanism of anti-atherosclerosis of vascular softening pills. Methods:Forty male ApoE~(-/-) mice were divided into 4 groups(model group, clopidogrel group, Vascular Softening Pills high dose group, Vascular Softening Pills low dose group), and another 10 C57 BL/6 mice were used as the control group. After 12 weeks intervention, the expressions of PAC-1 and CD40 L on blood lipids and peripheral platelets were measured and the pathological changes of aortic tissues were observed. The expression of CD40 L in aortic tissues was detected. Results:Compared with the model group, serum TC, TAG and LDL-C levels in the high dose group of Vascular Softening Pills and low dose Vascular Softening Pills group were significantly lower(P<0.05), and HDL-C levels were significantly higher(P<0.05). The degree of atherosclerotic lesions in the high dose group of Vascular Softening Pills and the low dose group of Vascular Softening Pills was significantly lower than that in the model group and clopidogrel group. The level of platelet activation markers in the two dose groups of Vascular Softening Pills was significantly higher than that in the model group. The decrease was observed(P<0.05). The optical density of CD40 L in the model group was significantly higher than that in the normal group(P<0.05). Conclusion:The mechanism of anti-atherosclerosis of Vascular Softening Pills may be related to regulating blood lipids and regulating the inhibition of platelet activation by CD40-CD40 L system.
引文
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[16] 孙丹,孙玉坤,惠福海.载脂蛋白E基因多态性与阿托伐他汀调脂疗效的相关性[J].沈阳药科大学学报,2011,28(2):157-161.
[17] Zhu W,Mix E,Jin T,et al.Bcellsplaya cooperative rolevia CD40L-CD40 interaction in Tcell-mediated experimental autoimmune neuritisin Lewisrats [J].Neurobiol Dis,2007,25(3):642-648.
[18] 张聪恪,李金环.血管软化丸降血脂作用的实验研究[J].中国医疗前沿,2007,8(4):21-23.
[19] 李金环.血管软化丸治疗高脂血症疗效观察[J].中国中医急症,2007,8(8):924,942.
[20] 刘建东,秦合伟.血管软化丸治疗急性脑梗死合并颈动脉粥样硬化斑块60例[J].中国民族民间医药,2017,18(9):88-91.
[21] 秦合伟,李彦杰,任锟,等.基于TLR9介导巨噬细胞极化效应探讨血管软化丸抗动脉粥样硬化的作用机制[J].中医药信息,2018,4(6):46-51.
[2] Robles-Carrillo L,Meyer T,Hatfield M,et al.Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice[J].J Immunol,2010,185(3):1577-1583.
[3] 刘建东,秦合伟.血管软化丸辅治脑梗死并颈动脉粥样硬化斑块对血流变和血清炎性因子的影响[J].实用中医药杂志,2018(1):44-46.
[4] V R Babaev,L Ding,J Reese,et al.Cyclooxygenase-1 Deficiency in Bone Marrow Cells Increases Early Atherosclerosis in Apolipoprotein E- and Low-Density Lipoprotein Receptor-Null Mice[J].Circulation,2006,113(1):108-117.
[5] Shim J,Al-Mashhadi R,Sorensen C,et al.Large animal models of atherosclerosis-new tools for persistent problems in cardiovascular medicine[J].J Pathol,2016,238(2):257-266.
[6] Boettger T,Braun T.A new level of complexity:the role of microRNAs in cardiovascular development[J].Circulation research,2012,110(7):1000-1013.
[7] Calkin AC,Drew BG,Ono A,et al.Reconstituted hish-density lipopmtein at-tenuntes platelet function in individuals with type 2 diabetes mefiitus by pmmoting cholesterol efiux[J].Cimulation,2013,120:2095-2104.
[8] Puecetti L,Pasqui AL,Pastorelli M,et al.Time.dependent efect of stutins on platelet function in hypereholestemlacmia[J].Eur J Clin Invest,2012,32:901-908.
[9] Massberg S,Brand K,Gruner S,et al.A criticalroh of platelet adhesionin the initiation of athemselemtic lesion formation[J].J Exp Med,2012,196:887-896.
[10] Buga GM,Navab M,Im aizumi S,et al.L-4F alt ers hyperlipidemic(but not health y) mouse plasma to reduce platelet aggregation[J].Arterioscler Thromb Vasc Biol,2014,30:283-289.
[11] 薛凌,邱雅慧,张扬,等.CD40-CD40L配体系统对兔动脉粥样硬化形成的影响[J].现代预防医学,2012,39(13):3318-3321.
[12] Stokes KY,Calahan L,Hamric CM,et al.CD40/CD40L contribute stohypercholesterolemia-induced microvascular inflammation [J].Am J Physiol Heart Circ Physiol,2009,296(3):689-697.
[13] Cholette JM,Blumberg N,Phipps RP,et al.Developmental changes in soluble CD40 ligand[J].J Pediatr,2008,152(1):50-54.
[14] Andre P,Nannizzi-Alaimo L,Prasad SK,et al.Platelet-derved CD40L:the switch-hitting player of cardiovascular disease [J].Circulation,2002,106(8):896-899.
[15] Antoniades C,Bakogiannis C,Tousoulis D,et al.The CD40/CD40 ligand system:linking inflammation with atherothrombosis [J].J Am Coll Cardiol,2009,54:669-677.
[16] 孙丹,孙玉坤,惠福海.载脂蛋白E基因多态性与阿托伐他汀调脂疗效的相关性[J].沈阳药科大学学报,2011,28(2):157-161.
[17] Zhu W,Mix E,Jin T,et al.Bcellsplaya cooperative rolevia CD40L-CD40 interaction in Tcell-mediated experimental autoimmune neuritisin Lewisrats [J].Neurobiol Dis,2007,25(3):642-648.
[18] 张聪恪,李金环.血管软化丸降血脂作用的实验研究[J].中国医疗前沿,2007,8(4):21-23.
[19] 李金环.血管软化丸治疗高脂血症疗效观察[J].中国中医急症,2007,8(8):924,942.
[20] 刘建东,秦合伟.血管软化丸治疗急性脑梗死合并颈动脉粥样硬化斑块60例[J].中国民族民间医药,2017,18(9):88-91.
[21] 秦合伟,李彦杰,任锟,等.基于TLR9介导巨噬细胞极化效应探讨血管软化丸抗动脉粥样硬化的作用机制[J].中医药信息,2018,4(6):46-51.
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