Calpain-1/NLRP3参与肺动脉高压进展和黄芪甲苷干预的机制研究

肺动脉高压（PAH）发病率高，预后差，且临床无特效药物，因此寻找PAH的新靶点和毒副作用小的中草药是当前该领域科研工作的重中之重。PAH始于炎症诱发的内皮损伤，发展于肺平滑肌细胞增殖。钙依赖性的半胱氨酸蛋白水解酶calpain-1和固有机体固有免疫成员NLRP3炎症小体都参与了肺动脉高压的内皮损伤，并在肺动脉高压患者身上有较高的表达，且在免疫细胞水平calpain-1可以激活NLRP3，因此我们推测calpain-1介导NLRP3激活诱发的炎症反应参与了PAH的发展。具有心血管保护作用的黄芪甲苷通过抑制calpain-1/NLRP3通路,抑制炎症反应,改善PAH症状。为此我们将采用现代分子生物手段，结合基因转染和基因敲除小鼠，观察calpain-1/NLRP3通路在PAH发展过程中的作用以及黄芪甲苷对该通路的调节，进一步阐明PAH发生发展机制，并为黄芪甲苷的合理开发提供科学的依据。

Pulmonary hypertension (PAH) has a high incidence, poor prognosis and no specific drugs in clinic. Therefore, finding new targets and Chinese herbal medicines with low toxicity and side effects of PAH is the most important research work in this field. PAH begins with inflammation-induced endothelial injury and develops with the proliferation of pulmonary smooth muscle cells. Calpain-1, a calcium-dependent cysteine proteolytic enzyme, and NLRP3 inflammatory body, an innate immune member of the body, are involved in the endothelial damage of pulmonary hypertension, and are highly expressed in patients with pulmonary hypertension. Calpain-1 can activate NLRP3 at the level of immune cells. Therefore, we speculate that calpain-1 mediates the inflammatory response induced by NLRP3 activation and participates in the development of PAH. Astragaloside IV has cardiovascular protective effect by inhibiting calpain-1/NLRP3 pathway, inhibiting inflammation and improving PAH symptoms. In order to further elucidate the mechanism of PAH occurrence and development, we will observe the role of calpain-1/NLRP3 pathway in the development of PAH and the regulation of Astragaloside IV on this pathway by modern molecular biological methods, combining gene transfection and gene knockout mice, and provide scientific basis for the rational development of Astragaloside IV.