Zhilong Huoxue Tongyu Capsule Ameliorates Platelet Aggregation and Thrombus Induced by Aspirin in Rats by Regulating Lipid Metabolism and MicroRNA Pathway

Introduction: Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. Objectives: This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. Methods: An AR model was established through treatment with a high-fat, high-sugar, and highsalt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6- keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA- 126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. Results: Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. Conclusion: This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.