目的观察芪丹通脉片(QDTMT)对心肌梗死后气虚血瘀证大鼠缺血心肌血管新生的作用及对HIF-1α、VEGF表达的影响。方法以结扎SD大鼠左冠状动脉前降支,制备急性心肌梗死模型,随机分为假手术(Sham)组、梗死组(MI)组、MI+芪丹通脉片小剂量(MI+QDTMTL)组和MI+芪丹通脉片大剂量(MI+QDTMTH)组。术后24h各组均用生理盐水配制成等体积药液灌胃,4周后动态评价各组大鼠气虚血瘀表征变化,采用免疫组化染色方法检测梗死边缘区CD31的表达,测定各组大鼠缺血心肌中新生血管数、微血管密度,于第7日、14日及28日时检测心梗边缘区HIF-1α和VEGFmRNA的表达。结果(1)Sham组无气虚血瘀证相关表现,而MI组、MI+QDTMTL组和MI+QDTMTH组都有气虚血瘀的相关表现,且MI组表现最为明显。(2)MI+QDTMTL组和MI+QDTMTH组CD31的表达较MI组增强,且MI+QDTMTH组高于MI+QDTMTL组。(3)与MI组相比.MI+QDTMTL组和MI+QDTMTH组心梗边缘区新生血管数及微血管密度增加,且MI+QDTMTH组高于MI+QDTMTL组。(4)RT—PCR结果显示,心梗后7d、14d时MI+QDTMTL组和MI+QDTMTH组HIF-1α mRNA及VEGFmRNA相对表达量较MI组增高.28d时MI+QDTMTL组和MI+QDTMTH组HIF-1α mRNA及VEGFmRNA相对表达量较MI组降低。结论QDTMT能够改善心梗大鼠气虚血瘀的症状,增加心梗边缘区新生血管数和微血管密度,调控HIF-1α与VEGFmRNA的表达,为心梗后心功能的改善提供了新的治疗思路.其机制可能与活化HIF-1α信号调控HIF-1α mRNA及VEGFmRNA的表达有关。
Objective: To study the effects of Qidantongmai Tablet on angiogenesis and expression of HIF-1α and VEGF in isehemic myoeardium of rats with myocardial infarction. Methods: Sprague-Dawley (SD) rats were subjected to MI by ligating the left anterior descending coronary and randomly divided into sham group,MI group ,low-dose QDTMT group (MI+QDTMTL) and high-dose QDTMT (MI+QDTMTH). After 24 hours of ligation, equal volume of liquid in each group was administrated with normal saline for 4 weeks. Qixuxueyu characterization changes of rats in each group were dynamicly evaluated after 4 weeks. The expression of CD31 in area at risk was measured by immunohistochemical methods,and Microvascular vascular count (MVC),Microvascular vascular density(MVD) in the ischemic myocardium were measured, at 7 d, 14 d and 28 d,the expression of HIF-1α mRNA and VEGFmRNA in the edge of infarc section were detected respectively. Results: (1)Qixuxueyu characterization changes: no Qixuxueyu disease-related performance of the sham group. But MI group,MI + QDTMTL group and MI+QDTMTH group has Qixuxueyu performance,and the performance of the MI group most obvious; (2)The expression of CD31 was higher in the MI+QDTMTL groups and the MI+QDTMTH group than the MI group,of which MI+QDTMTL group is less than MI+QDTMTH group. (3)Compared with the MI group,MVC and MVD in the edge of infarc section of the MI+QDTMTL group and the MI+QDTMTH group were significantly increased,of which the MI+QDTMTH group is higher than MI+QDTMTL group. (4)RT-PCR results showed that for the MI group, the expression of HIF-1α mRNA and VEGFmRNA of the MI+QDTMTL group and MI+QDTMTH group was increasing obviously at 7 d, 14 d after myocardial infarction, of which the MI+QDTMTL group and MI+ QDTMTH group was decreased at 28 d. Conclusion: Qidan Tongmai tablet can improve Qixuxueyu symptoms of MI rats,increase MVC and MVD in the edge of infarc section and regulate the expression of HIF-1α mRNA and