脑心通胶囊联合双联抗血小板疗法防治大鼠自体微血栓所致冠状动脉微栓塞(英文)

Chinese herbal medicine Naoxintong capsule combined with dual antiplatelet therapy in a rat model of coronary microembolization induced by homologous microthrombi

目的:探讨脑心通胶囊(Naoxintong capsule,NXT)联合双联抗血小板疗法(dual antiplatelet therapy,DA)对大鼠自体冠状动脉微栓塞(coronary microembolization,CME)的治疗效果。方法:在夹闭升主动脉的同时自心尖部注入同源大鼠微血栓(大鼠自体血凝块经38μm的滤网过滤制成)建立CME模型。95只大鼠不均等随机分成6组,即空白组(n=10)、假手术组(n=10)、CME组(n=15)、NXT组(n=15)、DA组(n=30)、NXT联合DA组(NDA组,n=15)。各组术前预给药3d,术后继续用药7d,取血后处死动物收集标本。共计69只大鼠获得完整数据。苏木精-伊红染色观察CME数量百分比(CME%),剪尾法检测出血时间(bleeding time,BT),玻片法检测凝血时间(clotting time,CT),比浊法检测二磷酸腺苷诱导的最大血小板聚集率(platelet aggregation rate,PAR),自动血液分析仪检测血小板计数,酶联免疫吸附试验法检测P选择素、白细胞介素6(interleukin-6,IL-6)、IL-10、内皮素1(endothelin-1,ET-1)及内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)。结果:与空白组及假手术组比较,CME组的CME%、PAR、P选择素、IL-6和ET-1明显升高(P<0.01),BT、CT、IL-10和eNOS明显降低(P<0.01);与CME组比较,各药物处理组的BT、CT、IL-10和eNOS明显升高(P<0.05或P<0.01),CME%、PAR、P选择素、IL-6和ET-1明显降低(P<0.05或P<0.01);其中DA组的BT和CT最长,PAR和P选择素最低,而NDA组的IL-10和eNOS最高,CME%、IL-6和ET-1最低;血小板计数在各组中无统计学差异(P>0.05)。结论:脑心通胶囊联合双联抗血小板治疗可能通过抑制血小板聚集、调节促炎因子与抗炎因子以及ET-1与eNOS的平衡显著减少CME模型大鼠的CME%。脑心通胶囊联合双联抗血小板治疗还能够减少双联抗血小板治疗出血的危险性。

Objective：In the present study,the efficacy of Naoxintong capsule （NXT）,a compound Chinese herbal medicine,combined with dual antiplatelet therapy （DA） in a rat model of coronary microembolization （CME） was evaluated. Methods：CME in rats was developed by injecting a suspension of microthrombotic particles into the left ventricle when the ascending aorta was obstructed. Microthrombotic particles were generated from the clots of rats sized by filtration through a screen （aperture diameter,38 μm）. A total of 95 rats were randomly divided into six groups,including control group,sham-operation （sham） group,CME model （CME） group,and NXT,DA,and NDA （NXT plus DA） groups. Rats in treatment groups were administered intragastrically with NXT,DA,and NDA,respectively,from 3 d before to 7 d after operation. All rats were sacrificed on day 7 post-operationally,and samples of blood and heart were collected. The complete data of 69 rats were obtained. The incidence of CME （CME%） was evaluated by hematoxylin-eosin staining. Bleeding time （BT） and clotting time （CT） were measured by means of tail cutting and glass slide methods,respectively. Adenosine diphosphate-induced maximum platelet aggregation rate （PAR） was assessed with turbidimetry. Platelet counts were examined by an automated hematology analyzer. The levels of serum P-selectin,interleukin （IL）-6,IL-10,endothelin （ET-1） and endothelial nitric oxide synthase （eNOS） were all detected by enzyme-linked immunosorbent assay. Results：Compared with control and sham groups,CME group had an increase in CME%,PAR,P-selectin,IL-6 and ET-1 （P〈0.01,P〈0.01）,and a decrease in BT,CT,IL-10 and eNOS （P〈0.01,P〈0.01）; compared with CME group,the groups receiving medications had an increase in BT,CT,IL-10 and eNOS （P〈0.05 or P〈0.01）,and a decrease in CME%,PAR,P-selectin,IL-6 and ET-1 （P〈0.05 or P〈0.01）,with DA group increasing most in BT and CT and decreasing most in PAR and P-selectin,and with NDA group increasing most in IL-10 and eNOS and decreasing most in CME%,IL-6 and ET-1. In terms of platelet counts,there was no statistically significant difference among groups （P〉0.05）.Conclusion：NXT combined with DA can decrease CME%. The probable mechanism is that this therapy can appropriately inhibit platelet aggregation,balance the pro-and anti-inflammatory cytokines as well as serum ET-1 and eNOS. This therapy can also reduce risk of intraoperative bleeding during DA therapy