敲除TSP1通过氨基酸和糖代谢通路对阿霉素所致心肌损伤的作用

目的 利用代谢组学方法阐明敲除血小板反应蛋白1(TSP1)通过调节小分子化合物的代谢，减轻阿霉素(ADM)致心肌损伤。方法 以24只野生型C57BL/6小鼠和24只TSP1基因敲除(TSP1^-/-)小鼠为实验对象，分为4组：WM组(n=12)、TSP1^-/-组(n=12)和WM-ADM组(n=12)、TSP1^-/--ADM组(n=12)。WM组和TSP1^-/-组小鼠腹腔注射生理盐水，WM-ADM组和TSP1^-/--ADM组小鼠腹腔注射ADM以建立慢性心功能衰竭(CHF)模型。以血清生化肌酸激酶(creatine kinase, CK)、肌酸激酶同工酶(creatine kinase isoenzymes, CK-MB)、乳酸脱氢酶(lactate dehydrogenase, LDH)]和心脏组织苏木精-伊红(hematoxylin-eosin, HE)染色为指标评价注射ADM后小鼠心肌损伤情况，以基于核磁共振(¹HNMR)的代谢组学技术来研究4组小鼠血...

Effects of knockout TSP1 on adriamycin induced myocardial injury through amino acids and glycose metabolism pathways

Objective To clarify that knockout of thrombospondins-1 (TSP1) can reduce myocardial injury caused by adriamycin (ADM) by regulating the metabolism of small molecular compounds. Methods In this study, 24 wild C57BL/6 mice and 24 knockout of TSP1 gene (TSP1-/-) mice were selected and divided into 4 groups (each n=12), mice in Group WM and Group TSP1-/- received normal saline intraperitoneal injection, and mice in Group WM-AMD and Group TSP1-/--AMD received ADM intraperitoneal injection. The myocardial injury of mice was evaluated by serum biochemistry for creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH), and HE staining of cardiac tissue after ADM injection. The changes of small molecule metabolites in serum of the 4 groups of mice were studied by metabolomics technology based on nuclear magnetic resonance (1HNMR). Results Serum biochemistry and HE staining of cardiac tissue showed that the cardiac tissue injury of TSP1-/- mice was significantly milder than that of wild mice after ADM injection. Metabonomics studies showed that knockout of TSP1 significantly affected amino acid metabolism in mice. The changes of serum leucine, isoleucine, valine, lactic acid, alanine, acetic acid and pyruvate were obvious in wild mice after ADM injection. The levels of serum metabolites in TSP1-/- mice were significantly reduced after ADM injection. Conclusion TSP1-/- mice may reduce the myocardial injury caused by ADM by regulating amino acid and glucose metabolism.