Xu Haibo, Wang Dejian, Peng Cheng, Huang Xiushen, Ou Ming, Wang Ningsheng, Wang Peixun, Zhou Lijuan, Ye Xiaolin
*Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; †Department of Pathology, College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China; ‡Department of Immunology, Institute of Clinical Pharmacology,Guangzhou University of Chinese Medicine, Guangzhou,China; and §Department of Pharmacology, Institute for Chinese Medical Research, Sichuan Academy of Chinese Medical Sciences, Chengdu, China.
J Cardiovasc Pharmacol. 2014 Apr;63(4):323-32. doi: 10.1097/FJC.0000000000000046.
The adherence to circulating leukocytes, such as monocytes and neutrophils, to vascular endothelial cells is of central importance to the pathogenesis of various cardiovascular diseases (CVDs) including atherosclerosis and myocardial ischemia-reperfusion injury. Compound danshen dripping pill (CDDP; Fufang Danshen Diwan in Chinese), namely cardiotonic pill, is extensively used for CVDs medication in China and some other countries. Here, we sought to investigate the effect of CDDP on leukocytes binding to vascular endothelial cells and elaborate the possibly underlying mechanism. Using seropharmacological method, rabbit sera containing CDDP were shown to mitigate the adhesiveness of monocytes and neutrophils to tumor necrosis factor alpha-stimulated human umbilical vein endothelial cells in dose and time-dependent manners, alleviate the levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 messenger RNA and protein dose dependently and also encumber IκBα degradation, p65 nuclear translocation, nuclear factor-kappaB (NF-κB) DNA-binding activity, and NF-κB-responsive gene transcription in tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This study suggests that CDDP protects against CVDs potentially by attenuation of leukocytes-endothelium adhesion cascade via lessening endothelial cell adhesion molecules expression and NF-κB signaling pathway activity.
循环白细胞(如单核细胞和中性粒细胞)与血管内皮细胞的黏附对于包括动脉粥样硬化和心肌缺血再灌注损伤在内的各种心血管疾病(CVD)的发病机制至关重要。复方丹参滴丸(CDDP;中文名为复方丹参滴丸),即强心丸,在中国和其他一些国家被广泛用于心血管疾病的治疗。在此,我们旨在研究CDDP对白细胞与血管内皮细胞结合的影响,并阐述其可能的潜在机制。采用血清药理学方法,含CDDP的兔血清可呈剂量和时间依赖性地减轻单核细胞和中性粒细胞与肿瘤坏死因子α刺激的人脐静脉内皮细胞的黏附性,剂量依赖性地降低细胞间黏附分子1和血管细胞黏附分子1信使核糖核酸及蛋白水平,还能抑制肿瘤坏死因子α激活的人脐静脉内皮细胞中IκBα降解、p65核转位、核因子κB(NF-κB)DNA结合活性及NF-κB反应性基因转录。本研究提示,CDDP可能通过减少内皮细胞黏附分子表达和NF-κB信号通路活性来减轻白细胞-内皮细胞黏附级联反应,从而对心血管疾病起到保护作用。