■本研究旨在探讨山丝氨酸对深静脉血栓形成(DVT)大鼠HUVEC细胞损伤和血栓形成的调节作用。并阐明潜在的分子机制。
使用超高效液相色谱系统VanquishUHPLC和质谱仪进行非靶向代谢组学数据分析以检测血浆代谢谱。进行转录组测序和基因干预实验以验证其调节作用。进行进一步的体内和体外实验。酶联免疫吸附试验检测P-选择素水平,E-选择素,和vWF,苏木精-伊红(HE)染色观察血栓及炎性细胞浸润,流式细胞术和TUNEL检测细胞凋亡,进行qPCR和WB测定以确定基因和蛋白质表达。
■Anseri减轻了HUVECs损伤,粘附分子表达减少,和炎症。它降低了P-选择素,E-选择素,vWF,THBD,TFPI级别,在促进HUVECs中NOS3,ET-1和NO释放的同时,细胞凋亡。在DVT大鼠中,山丝氨酸减少P-选择素,E-选择素,vWF,血栓形成,细胞浸润,凋亡,并促进不释放。转录组测序和基因干预证实了安丝氨酸对PI3K-Akt通路的调节和通过MYB的凝血。CARNMT1,一种羊膜代谢的调节酶,Anseri含量增加,抑制凝血,血栓形成,细胞浸润,并促进大鼠体内NO的释放。
■这项研究证实山丝氨酸可以通过改善炎症反应来缓解DVT,抑制血液凝集,促进血管舒张,提供新的潜在治疗靶点,DVT管理发展的重要科学证据,以及深入了解其分子机制的新线索。
UNASSIGNED: This study aimed to explore the regulatory effect of
anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.
UNASSIGNED: Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.
UNASSIGNED: Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats,
anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed
anserine\'s regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for
anserine metabolism, increased
anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.
UNASSIGNED: This study confirmed
anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.