摘要
目的:探究川陈皮素(CCPS)调节环鸟苷酸-腺苷酸合成酶(cGAS)-干扰素基因刺激蛋白(STING)信号通路对大鼠深静脉血栓(DVT)形成的治疗作用。方法:将大鼠随机分为假手术组、模型组、川陈皮素低剂量(CCPS-L)组、川陈皮素高剂量(CCPS-H)组、川陈皮素高剂量+cGAS-STING信号通路激活剂(DMXAA)(CCPS-H+DMXAA)组。全自动血凝分析仪检测血浆凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)水平、D-二聚体(D-dimer);全自动血液流变学仪测定大鼠血浆黏度和红细胞压积;ELISA检测肺组织中白细胞介素(IL)-1β(IL-1β)、IL-8、IL-10、肿瘤坏死因子-α(TNF-α)水平;H-E染色观察静脉血栓形成段的组织形态学;观察血栓形成情况;免疫印迹检测血管组织因子(TF)、组织因子途径抑制物(TFPI)、抗凝血酶(ATⅢ)、cGAS、STING蛋白表达。结果:与假手术组比较,模型组大鼠静脉管腔出现明显损伤,PT、APTT、TT、血清IL-10水平、下腔静脉组织ATⅢ蛋白表达水平显著降低,Fib和D-dimer水平、血浆黏度和红细胞压积水平、血清IL-1β、IL-8、TNF-α水平、血栓质量、下腔静脉组织TF、TFPI、cGAS、STING蛋白表达水平显著升高;与模型组相比,CCPS-L和CCPS-H组大鼠静脉管腔损伤明显减轻,PT、APTT、TT、血清IL-10水平、下腔静脉组织ATⅢ蛋白表达水平显著升高,Fib和D-dimer水平、血浆黏度和红细胞压积水平、血清IL-1β、IL-8、TNF-α水平、血栓质量、下腔静脉组织TF、TFPI、cGAS、STING蛋白表达水平显著降低;DMXAA可减弱川陈皮素对DVT大鼠的治疗作用。结论:川陈皮素可能通过抑制cGAS-STING信号通路降低炎症、改善凝血功能,进而抑制DVT形成。
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-αin 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),antithrombinⅢ(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 ATⅢprotein 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 ATⅢprotein 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.
作者
徐龙健
李彦辉
杨璇
王全力
张俐颖
Xu Longjian;Li Yanhui;Yang Xuan;Wang Quanli;Zhang Liying(Vascular Surgery Department,Tangshan Central Hospital,Tangshan 063000,China)
出处
《解剖学杂志》
2025年第2期128-132,共5页
Chinese Journal of Anatomy
