芪丹通脉片对动脉粥样硬化小鼠易损斑块及炎性因子的影响
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摘要
目的:从动脉粥样硬化斑块易损性及炎性反应角度,研究芪丹通脉片对动脉粥样硬化易损斑块的影响。方法:将36只Apo E-/-小鼠随机分为对照组(A组) 12只和手术组24只。手术组小鼠采用颈总动脉外置管术(PCCP)加高脂喂养制备动脉粥样硬化易损斑块模型;将手术组随机分为模型组(B组)和中药组(C组),每组12只。于造模后12周摘眼球取血,处死小鼠,截取右颈总动脉; ELISA法检测血清肿瘤坏死因子(TNF-α)、白介素-6 (IL-6)、C-反应蛋白(CRP)表达水平;苏木素-伊红染色(HE染色)研究斑块、脂质池情况以及结构;油红(oil red)染色检测斑块中脂质情况; Masson染色检测斑块胶原纤维蛋白情况; TUNEL染色检测血管平滑肌细胞凋亡情况。结果:与A组相比,B组小鼠TNF-α、IL-6、CRP水平显著升高(P<0. 01),药物干预后,C组小鼠TNF-α、IL-6、CRP水平较B组小鼠均显著降低(P<0. 01)。病理学分析发现,与B组相比,C组动脉内斑块数量,脂质池面积、数量,脂质含量、血管平滑肌细胞凋亡数量显著减少,斑块内胶原纤维蛋白含量显著增加,斑块趋于稳定。结论:炎症反应在动脉粥样硬化斑块易损化进程中扮演着重要角色,芪丹通脉片能显著下调动脉粥样硬化易损斑块模型小鼠机体炎性水平,通过减少动脉内斑块数量,脂质池数量、面积,脂质含量,血管平滑肌细胞凋亡数量,增加胶原纤维蛋白含量而降低斑块的易损性。
Objective: From the perspective of atherosclerotic plaque vulnerability and inflammatory response,the effect of Qidan Tongmai Tablet on vulnerable plaque of atherosclerosis was studied. Methods: 36ApoE-/-mice were randomly divided into controlled group(A group) with 12 animals and the surgical group with 24 animals. The surgical group of mice used Perivascular Carotid Collar Placement(PCCP) and Preparation of vulnerable atherosclerotic plaque model by high fat diet. The operation group was randomly divided into B: model group,C: Qidan Tongmai Tablet Group,each group with 12 mice. Twelve weeks after modeling,blood was taken from the eyeball,mice were killed,interception of the right common carotid artery. The serum levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and C-reactive protein(CRP) were detected by ELISA.Hematoxylin-eosin staining(HE staining) was used to study plaque,lipid pool conditions,and structure. Oil red staining was used to detect lipids in plaques. Masson staining was used to detect plaque collagen fibrin. TUNEL staining was used to detect the apoptosis of vascular smooth muscle cells. Results: Compared with group A,the levels of TNF-α,IL-6and CRP in group B were significantly increased(P<0. 05). After drug intervention,the levels of TNF-α,IL-6and CRP in the group C were significantly lower than those in the group B(P<0. 05). Pathological analysis showed that compared with the group B,plaque number,lipid pool area,number,lipid content,apoptosis of vascular smooth muscle cells in the group C were significantly reduced,and collagen fibrin content was significantly increased in the group C,Plaque tends to be stable. Conclusion: Inflammation plays an important role in the process of atherosclerotic plaque vulnerability. Qidan Tongmai Tablets can significantly reduce the inflammatory levels of atherosclerotic vulnerable plaque model mice,by reducing the number of plaques in the arteries,the number of lipid pools,area,lipid content,the number of apoptotic vascular smooth muscle cells,increase collagen fibrin content to decrease plaque vulnerability.
Objective: From the perspective of atherosclerotic plaque vulnerability and inflammatory response,the effect of Qidan Tongmai Tablet on vulnerable plaque of atherosclerosis was studied. Methods: 36ApoE-/-mice were randomly divided into controlled group(A group) with 12 animals and the surgical group with 24 animals. The surgical group of mice used Perivascular Carotid Collar Placement(PCCP) and Preparation of vulnerable atherosclerotic plaque model by high fat diet. The operation group was randomly divided into B: model group,C: Qidan Tongmai Tablet Group,each group with 12 mice. Twelve weeks after modeling,blood was taken from the eyeball,mice were killed,interception of the right common carotid artery. The serum levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and C-reactive protein(CRP) were detected by ELISA.Hematoxylin-eosin staining(HE staining) was used to study plaque,lipid pool conditions,and structure. Oil red staining was used to detect lipids in plaques. Masson staining was used to detect plaque collagen fibrin. TUNEL staining was used to detect the apoptosis of vascular smooth muscle cells. Results: Compared with group A,the levels of TNF-α,IL-6and CRP in group B were significantly increased(P<0. 05). After drug intervention,the levels of TNF-α,IL-6and CRP in the group C were significantly lower than those in the group B(P<0. 05). Pathological analysis showed that compared with the group B,plaque number,lipid pool area,number,lipid content,apoptosis of vascular smooth muscle cells in the group C were significantly reduced,and collagen fibrin content was significantly increased in the group C,Plaque tends to be stable. Conclusion: Inflammation plays an important role in the process of atherosclerotic plaque vulnerability. Qidan Tongmai Tablets can significantly reduce the inflammatory levels of atherosclerotic vulnerable plaque model mice,by reducing the number of plaques in the arteries,the number of lipid pools,area,lipid content,the number of apoptotic vascular smooth muscle cells,increase collagen fibrin content to decrease plaque vulnerability.
引文
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[2]刘雅,肖茜,王超.等.芪丹通脉片治疗动脉粥样硬化的效果[J].心脏杂志,2008,20(3):244
[3]魏裕红.芪丹通脉片治疗冠心病心绞痛(气虚血瘀证)的Ⅲ期临床研究[D].成都中医药大学,2008
[4]谢娟,王宗仁,宋铁兵,等.芪丹通脉片促进骨髓间充质干细胞向缺血心肌趋化迁移[J].现代生物医学进展,2012,12(9):1613~1617
[5]闫浩.胰岛素对不稳定斑块形成的影响及机制的研究[D].第四军医大学,2013
[6]马湉.不同CD4+T细胞亚群对动脉粥样硬化斑块易损性和斑块破裂的影响及其机制研究[D].山东大学,2011
[7] Andrew Moran,Dongfeng Gu,Dong Zhao,et al. Future cardiovascular disease in china:markov model and risk factor scenario projections from the coronary heart disease policy model-china.[J]. Circulation. Cardiovascular quality and outcomes,2010,3(3):243~252
[8]赵爱梅,任钧国,刘建勋.益气活血方治疗冠心病气虚血瘀证作用机制研究进展[J].中国实验方剂学杂志,2017,23(7):215~220
[7]马爱玲.芪丹通脉片对大鼠动脉粥样硬化的防治作用及其对ICAM-1、VCAM-1、e NOS mRNA表达的影响[D].第四军医大学,2004
[8]李建军.炎症与动脉粥样硬化[J].中国医学前沿杂志(电子版),2011,3(5):4~6
[9]马爱玲.芪丹通脉片对大鼠动脉粥样硬化的防治作用及其对ICAM-1、VCAM-1、e NOS mRNA表达的影响[D].第四军医大学,2004
[10]李建军.炎症与动脉粥样硬化[J].中国医学前沿杂志(电子版),2011,3(05):4~6
[11] Norata GD,Ballantyne CM,Catapano AL. New therapeutic principles in dyslipidaemia:focus on LDL and Lp(a)lowering drugs[J]. Eur Heart J,2013,34(24):1783~1789
[12] Clarke MC,Littlewood TD,Figg N,et al. Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration[J]. Circ Res, 2008, 102(12):1529~1538
[13] Bjorkbacka H. Atherosclerosis:cell biology and lipoproteins[J]. Curr Opin Lipidol,2011,22(1):74~75
[14]郑俊华,刘艳阳.血清炎性因子与急性冠状动脉综合征易损斑块相关性的研究进展[J].医学综述,2017,23(01):129~133
[15]杨俊,岳增辉,谢涛,等.动脉粥样硬化易损斑块与TLR4/NF-κB信号通路关系的研究进展[J].中西医结合心脑血管病杂志,2014,12(06):747~749