Regulation of Autophagy by Tetramethylpyrazine Through the PI3K/AKT/mTOR Pathway to Treat Pulmonary Thromboembolism

Thrombus formation is the primary cause of pulmonary thromboembolism (PTE), and the effective treatment of thrombus can significantly reduce the harm associated with PTE. Tetramethylpyrazine (TMP) demonstrates good antithrombotic activity, but its therapeutic effect on PTE and the underlying mechanism remains unclear. To elucidate the mechanism underlying TMP's antithrombotic activity, a hypoxic-induced PVSMCs model was established. The levels of ROS in PVSMCs were effectively reduced by TMP. Furthermore, the expression of LC3II and Beclin-1 was downregulated. Additionally, PI3K expression was downregulated and mTOR phosphorylation was promoted by TMP. Subsequently, a PTE rat model was established, and TMP intervention was administered via intraperitoneal injection. It was observed that lung injury and oxidative stress were effectively alleviated by TMP. Meanwhile, the expression of LC3 and Beclin-1 was also inhibited by TMP, leading to a reduction in cell apoptosis. In conclusion, by inhibiting the PI3K/AKT/mTOR pathway, TMP inhibited hypoxia-induced excessive autophagy, exerting its therapeutic activity against PTE. This finding provided a potential and readily translatable therapeutic strategy for the clinical treatment of PTE.