Zhilong Huoxue Tongyu capsule ameliorates platelet aggregation and thrombus induced by aspirin in rats by regulating lipid metabolism and microRNA pathway.

Abstract

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. This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. An AR model was established through treatment with a high-fat, high-sugar, and high-salt 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), low-density 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 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. This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.