益气活血方对气虚血瘀型冠心病模型大鼠的影响研究

目的探讨益气活血方对气虚血瘀型冠心病模型大鼠的影响。方法32只SD大鼠随机分为空白组、模型组、益气活血方组和芪参益气滴丸组,每组8只。除空白组外,各组均采用“游泳力竭+控制饮食+结扎冠状动脉左前降支”制备病证结合气虚血瘀型冠心病动物模型,时间均为11 d。造模结束后,分别灌胃予以相应干预14 d。采集大鼠心电图,进行Morris水迷宫、旷场实验并HE染色、Masson染色,并采用ELISA检测血浆纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)、血管性假血友病因子(von Willebrand factor,vWF)、组织型纤溶酶原激活剂(tissue-type plasminogenactivator,t-PA)的含量。结果与空白组比较,模型组心电图ST段抬高;Morris水迷宫实验潜伏期延长(P<0.01),穿台次数显著减少(P<0.01);旷场实验水平得分、垂直得分减少(P<0.05),中心活动时间延长(P<0.05),角落活动时间、周边活动时间均减少,焦虑程度降低(P<0.05或P<0.01);心肌细胞排列较紊乱,在梗死灶周围出现核破裂,血浆中PAI-1、vWF水平明显增高(P<0.05或P<0.01),t-PA水平明显降低(P<0.05)。与模型组比较,益气活血方组心电图ST段恢复正常;Morris水迷宫潜伏期显著缩短(P<0.01),穿台次数显著增加(P<0.01);旷场实验中心活动时间减少(P<0.05),角落活动时间延长(P<0.05),焦虑程度增高(P<0.05);梗死灶周围心肌细胞排列整齐,心肌细胞凋亡指数降低(P<0.05);血浆中PAI-1、vWF水平均降低(P<0.05或P<0.01),t-PA水平增高(P<0.05)。结论病证结合动物模型更能满足中西医结合研究的需要;益气活血方能有效修复气虚血瘀型冠心病模型大鼠心肌细胞损伤并改善记忆力减退、健忘、疲劳及反应迟钝的症状,且改善高凝状态的机制与调节vWF、PAI-1、t-PA水平有关。

Effects of Yiqi Huoxue Formula on Coronary Heart Disease Rats with Qi Deficiency and Blood Stasis Syndrome

Objective To explore the effects of Yiqi Huoxue Formula on the model rats of coronary heart disease with Qi deficiency and blood stasis.Methods A total of 32 SD rats were randomly divided into a blank group,a model group,a Yiqi Huoxue Formula group and a Qishen Yiqi dropping pill group,with 8 rats in each group.Except for the blank group,each group used"swimming exhaustion+diet control+ligation of left anterior descending branch of coronary artery"to prepare the animal model of coronary heart disease combined with Qi deficiency and blood stasis syndrome,and the duration was 11 days.At the end of modeling,the drugs were given by gavage for 14 days.ECG of rats were obtained.Morris water maze,open field test,HE staining and Masson staining were performed.The contents of plasminogen activator inhibitor(PAI-1),von Willebrand factor(vWF),tissue plasminogen activator(t-PA)were measured by ELISA.Results Compared with the blank group,ST segment of ECG in the model group was elevated;in the Morris water maze experiment,the latency was prolonged(P<0.01),and the number of platform penetration was significantly shortened(P<0.01);For the open field experiment,the horizontal score and vertical score were decreased(P<0.05),and the central activity time was prolonged(P<0.05).The corner activity time,the peripheral activity time,and the degree of anxiety were decreased(P<0.05 or P<0.01);the arrangement of myocardial cells was more disordered,with nuclear rupture around the infarct.In the plasma,the expression of PAI-1,vWF were significantly increased(P<0.05 or P<0.01)and t-PA was decreased(P<0.05).Compared with the model group,ST segment of ECG in Yiqi Huoxue Formula group returned to normal,and the latency of Morris water maze was significantly shortened(P<0.01).The times of platform penetration was significantly prolonged(P<0.01),and the central activity time of open field experiment was decreased(P<0.05).The activity time of corner was prolonged(P<0.05),and the anxiety degree was increased(P<0.05).The arrangement of myocardial cells around the infarct was orderly,and the apoptosis index of myocardial cells was decreased(P<0.05).The PAI-1 and vWF levels in plasma were decreased(P<0.05 or P<0.01).The level of t-PA increased(P<0.05).Conclusion The animal model of the combination of disease and syndrome can better meet the needs of the study of the combination of traditional Chinese and western medicine.Yiqi Huoxue Formula can effectively repair the myocardial cell injury of the model of coronary heart disease of Qi deficiency and blood stasis,improve the symptoms of memory loss,forgetfulness,fatigue and slow response,and the mechanism of improving the hypercoagulable state is related to the regulation of vWF,PAI-1 and t-PA levels.