Effect of Xuefu Zhuyu Capsule (血府逐瘀胶囊) on the Symptoms and Signs and Health-related Quality of Life in the Unstable Angina Patients with Blood-stasis Syndrome after Percutaneous Coronary Intervention: A Randomized Controlled Trial

Objective： Compared with Shengmai Capsule （生脉胶囊, SM）, the study was conducted to evaluate the efficacy and safety of Xuefu Zhuyu Capsule （血府逐瘀胶囊, XFZY） on the symptoms and signs and health-related quality of life （HR-QOL） in the unstable angina （UA） patients with blood-stasis syndrome （BSS） after percutaneous coronary intervention （PCI）. Methods： A randomized, double-blinded, doubledummy, and placebo-controlled trial was applied. Ninety patients, diagnosed as UA and BSS after successful PCI, were enrolled and equally randomized into three groups, XFZY group, SM group, and placebo group, and administered with the corresponding medications respectively for four weeks. The clinical symptoms and signs （CSS）, electrocardiography （ECG）, and BSS scores were recorded and compared among groups during and after the treatment. Short-form 36 （SF-36） and Seattle Angina Questionnaire （SAQ） were applied to assess the HR-QOL in each group before and after the treatment. Safety indexes （blood routine and liver and kidney function tests） were also examined at the beginning and after the treatment. Results： Eighty-six patients completed the whole study. After the treatment, the total effective rates of the XFZY group in ameliorating CSS and ECG were 76.7% and 60.0%, respectively, which were obviously higher than those in SM （CSS： 53.3%; ECG： 36.7%） and the placebo （CSS： 43.3%; ECG： 30.0%） groups. After one week＇s treatment, BSS scores slightly decreased in each group, but no significant differences were found among three groups （P0.05）. After four weeks＇ treatment, BSS scores in the XFZY group decreased to a lower level compared with SM （P0.05） and the placebo （P0.01） groups. After the treatment, the efficacy of XFZY group in improving body pain （BP）, general health （GH）, vitality （VT）, society functioning （SF）, role emotional （RE）, angina stability （AS）, angina frequency （AF）, and treatment satisfaction （TS） were better than those in the placebo group （P0.05, P0.01）. Meanwhile, the dimensions of BP, GH, SF, AS, AF, and TS were better improved than those in the SM group （P0.05）. No obvious adverse reaction was found during and after the treatment except one case in the XFZY group reporting of stomach discomfort. Conclusions： Compared with SM Capsule treatment, a short-term treatment with XFZY Capsule exhibits better efficacy on CSS and BSS scores, and HR-QOL in UA patients with BSS after PCI. However, its long-term efficacy and safety still needs further investigation.

Effect of Xuefu Zhuyu Capsule (血府逐瘀胶囊) on Angiogenesis in Hindlimb Ischemic Rats

Objective:To investigate the effect and mechanism of Xuefu Zhuyu Capsule(血府逐瘀胶囊,XZC)on pro-angiogenesis in the hindlimb ischemic model rats.Methods:A total of 100 Sprague Dawley rats were randomly divided into a model group,a regular-dose XZC group(0.48 g·kg^-1·d^-1)and a high-dose XZC group(0.96 g·kg^-1·d^-1)using random number table method.The model of hindlimb ischemic rats were made through femoral artery embolization with Bletilla microsphere age nt.XZC were give n on the first day after embolization surgery and lasted 5 days.Finally 72 models were obtained with 12 in each group for each time point.The lower Ischemic limb was amputated on the third day after embolization surgery.Histopathological characters and the number of blood vessels of granulation tissues were observed at 36 and 48 h after amputation,respectively.The main genes were obtained from microarray analysis and were validated using real-time quarttitative polymerase chain reaction.Results:The vascular number of granulation tissues at both 36 and 48 h were characterized by new and fresh vessels.The number of angiogenesis in the high-dose XZC group at 36 and 48 h was greater compared with that in the regular-dose XZC and model groups(P<0.01),and high-dose XZC at 36 h increased more vessels than that at 48 h(P<0.01).Consequently,granulation tissues from the high-dose XZC group at 36 h were chosen for microarray analysis.In all,2,085 differentially expressed genes(DEGs)were detected and 25 DEGs were determined to be directly related to an giogenesis.Four biological process terms were found including an giogenesis,regulati on of an gioge nesis,positive regulati on of an giogenesis,and positive regulation of vascular end othelial growth factor receptor sign aling pathway(P<0.05).Microarray an alysis also showed 49 pathways including 11 pathways related to an giogenesis.Conclusion:XZC promoted angiogenesis moderately and the mechanism invoIved multiple DEGs and multiple pathways.

Effect of EphB4/EphrinB2 Reverse Signal on Angiogenesis Induced by Xuefu Zhuyu Capsule(血府逐瘀胶囊) Containing Serum in Human Microvascular Endothelial Cell 1

Objective： To evaluate the effect of Xuefu Zhuyu Capsule（血府逐瘀胶囊）-containing serum（XFZY-CS） on Eph B4/ephrin B2 and its reverse signal in human microvascular endothelial cell-1（HMEC-1）. Methods： XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on Eph B4/ephrin B2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confirmed the results through activating and inhibiting the reverse signal by Eph B4/fc and pyrophosphatase/phosphodiesterase2（PP2）. Results： XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of Eph B4-m RNA at 12 h（P〈0.05）, and down-regulates its expression at 24 h（P〈0.01）. Protein expression of Eph B4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrin B2 increased at 9 h（P〈0.05）. In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator Eph B4/Fc ranging from 0.5 to 5 μg/m L（P〉0.05）. XFZY-CS also reduced the inhibitive effect of PP2 in limited periods. Conclusion： Eph B4/ephrin B2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY＇s effect on promoting angiogenesis.