Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China; Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China.
Biomed Pharmacother. 2022 Jul;151:113198. doi: 10.1016/j.biopha.2022.113198. Epub 2022 May 28.
Leptospirosis, caused by pathogenic leptospira, is a neglected infectious disease that causes acute kidney injury, bleeding disorders, and even death. People can become infected with leptospirosis when they travel into epidemic areas. Except for vaccines and antibiotics, there are few reports of other drugs about prevention of leptospirosis. In this study, we show that the natural molecular compound, astragalus polysaccharides (APS), prevents against acute leptospirosis in hamsters. Pretreatment with APS improved the survival rate of hamsters with more minor organ damage and lower leptospira burden. After pretreatment with APS, the expression levels of leptospira-induced TLR2, TLR4, and TNF-α were enhanced. The priming effect of APS was studied in vitro. The data showed that leptospira-induced expressions of TNF-α and IL-1β were higher in APS-primed peritoneal macrophage, with enhanced glucose consumption and lactate production. Transcriptomic analysis revealed that pretreatment with APS down regulated respiratory chain and mitochondrial function, up regulated glycolysis related gene expressions. After pretreatment with glycolysis inhibitor (2-DG), the priming effect of APS in leptospira infection was inhibited. Our results indicated that pretreatment with natural molecular compound, APS, protected against acute leptospirosis in hamsters by priming effect through enhanced glycolysis.
钩端螺旋体病是由致病性钩端螺旋体引起的一种被忽视的传染病，可导致急性肾损伤、出血性疾病，甚至死亡。人们在进入疫区时可能会感染钩端螺旋体病。除了疫苗和抗生素外，关于预防钩端螺旋体病的其他药物报道很少。在这项研究中，我们表明天然分子化合物黄芪多糖（APS）可预防仓鼠的急性钩端螺旋体病。APS 预处理可提高仓鼠的生存率，减少器官损伤和降低钩端螺旋体负担。APS 预处理后，钩端螺旋体诱导的 TLR2、TLR4 和 TNF-α 的表达水平增强。体外研究了 APS 的引发作用。结果表明，APS 预处理可增强 LPS 诱导的 TNF-α 和 IL-1β的表达，增加葡萄糖消耗和乳酸生成。转录组分析表明，APS 预处理可下调呼吸链和线粒体功能，上调糖酵解相关基因的表达。用糖酵解抑制剂（2-DG）预处理后，抑制了 APS 在钩端螺旋体感染中的引发作用。我们的结果表明，天然分子化合物 APS 通过增强糖酵解的引发作用，可预防仓鼠的急性钩端螺旋体病。
