养心颗粒对易损斑块Rho/Rho激酶信号通路血清IL-1、MCP-1和AngⅡ表达的影响
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摘要
目的观察养心颗粒对易损斑块Rho/Rho激酶信号通路血清白细胞介素-1(IL-1)、单核细胞趋化蛋白-1(MCP-1)及血管紧张素Ⅱ(AngⅡ)含量的影响。方法随机将雄性家兔分为模型对照组、养心颗粒组和法舒地尔组,每组8只,并给予高脂饮食喂养8周,空白对照组则选用同系家兔8只,予普通喂养。2周药物治疗后通过ELISA法测定IL-1、MCP-1及AngⅡ的浓度,并测定斑块面积(PA)与管腔面积(LA)之比。结果与空白组比较,模型组颈总动脉PA/LA比值升高(P <0.05),IL-1、MCP-1、AngⅡ浓度均显著升高(P <0.05);与模型组比较,养心颗粒组和法舒地尔组颈总动脉PA/LA比值降低(P <0.05),IL-1、MCP-1、AngⅡ浓度明显降低(P <0.05)。经相关性分析,IL-1、MCP-1、AngⅡ表达水平两两呈正相关(P <0.05),相关系数(r)分别为0.549、0.493和0.747。结论养心颗粒可通过调控Rho/Rho激酶信号通路降低血清IL-1、MCP-1及AngⅡ的表达水平,这可能是其抑制炎症反应而实现稳定易损斑块的作用机制。
Objective: To investigate the effect of Yangxin Granules on serum IL-1,MCP-1 and AngⅡ content of Rho/rho kinase signaling pathway in vulnerable plaque. Methods: The male rabbits were randomly divided into the model group,Yangxin Granules group and Fasudil group. In each group,8 were given a high-fat diet for8 weeks. In the blank group,8 rabbits were selected for common feed. The content of IL-1,MCP-1 and AngⅡwas determined by Elisa method after 2 weeks of treatment,and the ratio of plaque area and lumen area were measured. Results: Compared with the blank group,the PA/LA ratio of the common carotid arteries increased and IL-1,MCP-1 and AngⅡ concentrations increased significantly in the model group(P < 0.05). Compared with the model group,the PA/LA ratio decreased,as well as IL-1,MCP-1 and AngⅡ concentrations in Yangxin Granules groups and Fasudil group(P < 0.05). After correlation analysis,the expression level of IL-1,MCP-1 and AngⅡwas positively correlated(P < 0.05),and the correlation coefficients(r) were 0.549,0.493 and 0.747 respectively.Conclusion: Yangxin Granules can reduce the expression level of serum IL-1,MCP-1 and AngⅡ by modulating Rho/rho kinase signaling pathway,which may be the mechanism of inhibiting inflammatory response and achieving stable and vulnerable plaque.
Objective: To investigate the effect of Yangxin Granules on serum IL-1,MCP-1 and AngⅡ content of Rho/rho kinase signaling pathway in vulnerable plaque. Methods: The male rabbits were randomly divided into the model group,Yangxin Granules group and Fasudil group. In each group,8 were given a high-fat diet for8 weeks. In the blank group,8 rabbits were selected for common feed. The content of IL-1,MCP-1 and AngⅡwas determined by Elisa method after 2 weeks of treatment,and the ratio of plaque area and lumen area were measured. Results: Compared with the blank group,the PA/LA ratio of the common carotid arteries increased and IL-1,MCP-1 and AngⅡ concentrations increased significantly in the model group(P < 0.05). Compared with the model group,the PA/LA ratio decreased,as well as IL-1,MCP-1 and AngⅡ concentrations in Yangxin Granules groups and Fasudil group(P < 0.05). After correlation analysis,the expression level of IL-1,MCP-1 and AngⅡwas positively correlated(P < 0.05),and the correlation coefficients(r) were 0.549,0.493 and 0.747 respectively.Conclusion: Yangxin Granules can reduce the expression level of serum IL-1,MCP-1 and AngⅡ by modulating Rho/rho kinase signaling pathway,which may be the mechanism of inhibiting inflammatory response and achieving stable and vulnerable plaque.
引文
[1]陈伟伟,高润霖,刘力生,等.中国心血管病报告2017概要[J].中国循环杂志,2018,33(1):1-8.
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[13] Sun Z,Wu X,Li W,et al. RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels[J]. BMC Cardiovasc Disord,2016,16(1):193.
[14] Huang L,Li Q,Wen R,et al. Rho-kinase inhibitor prevents acute injury against transient focal cerebral ischemia by enhancing the expression and function of GABA receptors in rats[J]. Eur J Pharmacol,2017(797):134-142.
[15]吴俊,刘建全,李慧萍,等.肺炎衣原体感染促进APOE小鼠动脉粥样硬化研究[J].中华医院感染学杂志,2015,25(20):4630-4632.
[16]汪丽丽,贺钰梅,张永莉.急性心肌梗死患者血清超敏C反应蛋白、单核细胞趋化蛋白-1表达及临床意义[J].国际检验医学杂志,2017,38(9):1259-1261.
[17]朱玉洁,仲琳,杨军.半乳糖凝集素-3、白介素-6、单核细胞趋化蛋白-1与动脉粥样硬化斑块稳定性的相关性研究[J].解放军医药杂志,2017,29(12):39-41.
[18] De Silva TM,Kinzenbaw DA,Modrick ML,et al. Heterogeneous impact of ROCK2 on carotid and cerebrovascular function[J]. Hypertension,2016,68(3):809-817.
[19]徐敏,韦舒杰,张彦,等. ApoE缺陷大鼠动脉粥样硬化模型的构建[J].中国动脉硬化杂志,2017,25(1):78-82.
[2] Tousoulis D,Oikonomou E,Economou EK,et al. Inflammatory cytokines in atherosclerosis:Current thera peutic approaches[J]. Eur Heart J,2016,37(22):1723-1732.
[3]赵经纬,孙鹿璐,张红珍. Rho/Rho激酶信号通路与动脉粥样硬化关系的探讨[J].中华中医药杂志,2018,33(1):209-211.
[4]王新,李春阳,苏立平,等.动脉粥样硬化发病机制及治疗的进展[J].实用心脑肺血管病杂志,2017,25(2):1-4.
[5]张琪,郭子怡,翟文姬.养心颗粒对心力衰竭大鼠AngII和ET-1的影响[J].时珍国医国药,2017,28(10):2366-2368.
[6] Timmins LH,Molony DS,Eshtehardi P,et al. Oscillatory wall shear stress is a dominant flow characteristic affecting lesion progression patterns and plaque vulnerability in patients with coronary artery disease[J]. J R Soc Interface,2017,14(127):20160972.
[7]周光妍,于波.冠状动脉易损斑块形成机制研究进展[J].中华老年多器官疾病杂志,2018,17(2):153-155.
[8]孙秀玲,姜明霞.黄芪药理作用机制的研究进展[J].中医临床研究,2015,7(17):140-141.
[9]代晓光,宋琳.五味子现代药理作用及临床应用研究进展[J].中医药信息,2017,34(5):121-124.
[10]任浩,王琳,刘宵,等. Ras同源基因家族蛋白A/Rho相关卷曲螺旋蛋白激酶信号通路与脑梗死关系的研究进展[J].中国脑血管病杂志,2017,14(11):603-607.
[11] Smithers CC,Overduin M. Structural mechanisms and drug discovery prospects of Rho GTPases[J]. Cells,2016,5(2):E26.
[12] Ruihua H,Mengyi Z,Chong Z,et al. RhoA regulates resistance to irinotecan by regulating membrane transporter and apoptosis signaling in colorectal cancer[J]. Oncotarget,2017,7(52):87136-87146.
[13] Sun Z,Wu X,Li W,et al. RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels[J]. BMC Cardiovasc Disord,2016,16(1):193.
[14] Huang L,Li Q,Wen R,et al. Rho-kinase inhibitor prevents acute injury against transient focal cerebral ischemia by enhancing the expression and function of GABA receptors in rats[J]. Eur J Pharmacol,2017(797):134-142.
[15]吴俊,刘建全,李慧萍,等.肺炎衣原体感染促进APOE小鼠动脉粥样硬化研究[J].中华医院感染学杂志,2015,25(20):4630-4632.
[16]汪丽丽,贺钰梅,张永莉.急性心肌梗死患者血清超敏C反应蛋白、单核细胞趋化蛋白-1表达及临床意义[J].国际检验医学杂志,2017,38(9):1259-1261.
[17]朱玉洁,仲琳,杨军.半乳糖凝集素-3、白介素-6、单核细胞趋化蛋白-1与动脉粥样硬化斑块稳定性的相关性研究[J].解放军医药杂志,2017,29(12):39-41.
[18] De Silva TM,Kinzenbaw DA,Modrick ML,et al. Heterogeneous impact of ROCK2 on carotid and cerebrovascular function[J]. Hypertension,2016,68(3):809-817.
[19]徐敏,韦舒杰,张彦,等. ApoE缺陷大鼠动脉粥样硬化模型的构建[J].中国动脉硬化杂志,2017,25(1):78-82.