Establishment of CME Mouse Model Based on Autologous Thrombotic Particles and the Effect of Shexiang Tongxin Dropping Pill on the Coronary Microvascular Blood Flow in This Model

Abstract

Coronary microvascular disease poses significant clinical harm and is closely associated with major cardiovascular adverse events. Existing research has highlighted coronary microvascular embolism (CME) as an important factor. Previous studies have utilized microspheres to construct a mouse model of CME, which can partially simulate coronary microvascular disease. However, there are notable discrepancies from the clinical reality. Shexiang Tongxin Dropping Pill (SXDP), a traditional Chinese patent medicine, is widely used in Chinese hospitals for treating coronary heart disease. Our preliminary research has indicated that SXDP effectively alleviates chest pain symptoms and improves coronary thrombolysis in myocardial infarction (TIMI) blood flow in patients with angina pectoris. Nonetheless, the specific mechanism remains unclear. To address this, the current study aimed to explore the size and concentration of autologous thrombotic particles to construct a CME mouse model, taking reference from previous studies on microsphere parameters (size: 9 µm; concentration: 500 000/50 µl). Additionally, we aimed to observe the effect of SXDP on coronary microvascular blood flow in this model. The experiments revealed that the average size of 400-mesh thrombus particles closely approximated 9 µm, and the concentration suspension at a ratio of 1 : 0.15, with a volume of 50 µl, contained approximately 500 000 particles. Concurrently, we observed that 400-mesh blood clot particles induced T-wave elevation in the electrocardiogram, decreased region of interest value in laser speckle examination, downregulated CD31 and Lectin in vascular endothelium, caused thrombosis in coronary microvessels, and led to myocardial infarction. Moreover, a decrease in serum nitric oxide levels and an increase in endothelin-1 (ET-1) were observed. Furthermore, we investigated the effects of SXDP on this animal model and identified potential mechanisms underlying its ability to reverse the aforementioned pathological changes. The research findings suggest that 400-mesh blood clot particles can successfully establish a CME mouse model, and SXDP can improve coronary microvascular blood perfusion, potentially through the improvement of endothelial function.