Abstract
Objective:To investigate the therapeutic effect of Nobiletin(CCPS)on deep vein thrombosis(DVT)in rats by regulating the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.Methods:Rats were randomly grouped into sham operation group,model group,low-dose Nobiletin(CCPS-L)group,high-dose Nobiletin(CCPS-H)group,and high-dose Nobiletin+cGAS-STING signaling pathway activator(CCPS-H+DMXAA)group.Fully automatic coagulation analyzer was applied to detect plasma prothrombin time(PT),activated partial prothrombin time(APTT),thrombin time(TT),fibrinogen(Fib)levels,and D-dimer.Fully automatic blood rheometer was utilized to measure rat plasma viscosity and hematocrit.ELISA was adopted to detect the levels of IL-1β,IL-8,IL-10,and TNF-α in lung tissue.H-E staining was used to observe the tissue morphology of venous thrombotic segments.Western blotting was employed to detect vascular tissue factor(TF),tissue factor pathway inhibitor(TFPI),antithrombin Ⅲ(ATⅢ),cGAS,and STING protein expression.Results:Compared with the sham operation group,the venous lumen of rats in the model group showed obvious damage.The PT,APTT,TT,the level of serum IL-10,and the expression level of ATⅢ protein in the inferior vena cava tissue were significantly reduced,while the levels of Fib and D-dimer,plasma viscosity and hematocrit,the levels of serum IL-1β,IL-8,TNF-α,thrombus mass,the protein expression levels of TF,TFPI,cGAS,and STING in the inferior vena cava tissue were significantly increased.Compared with the model group,the venous lumen injury of rats in the CCPS-L and CCPS-H groups was significantly reduced,while the PT,APTT,TT,the level of serum IL-10,and the expression level of ATⅢ protein in the inferior vena cava tissue were significantly increased.The levels of Fib and D-dimer,plasma viscosity and hematocrit,the levels of serum IL-1β,IL-8,TNF-α,thrombus mass,the protein expression levels of TF,TFPI,cGAS,and STING in the inferior vena cava tissue were significantly reduced.DMXAA attenuated the effect of Nobiletin on DVT rats.Conclusion:Nobiletin may reduce inflammation,improve coagulation function,and inhibit DVT formation by inhibiting the cGAS-STING signaling pathway.关键词
川陈皮素/环鸟苷酸-腺苷酸合成酶/干扰素基因刺激蛋白/深静脉/血栓/大鼠Key words
Nobiletin/cyclic GMP-AMP synthase/stimulator of interferon genes/deep vein/thrombosis/rat分类
基础医学
