基于NF-κB/COX-2通路探讨桃红四物汤对大鼠下肢深静脉血栓形成的影响OA
A Study on the Effects of Taohong Siwu Decoction on Lower Extremity Deep Vein Thrombosis of Rats via the NF-κB/COX-2 Pathway
目的:基于核转录因子 κB(NF-κB)/环氧合酶-2(COX-2)通路探讨桃红四物汤(TH-SWD)对大鼠下肢深静脉血栓形成(LEDVT)的影响.方法:构建 LEDVT 大鼠模型,成功建模的大鼠随机分为 LEDVT 组、桃红四物汤低剂量组(L-THSWD 组)、桃红四物汤高剂量组(H-THSWD 组)、NF-κB抑制剂组(BAY11-7082 组)、桃红四物汤高剂量+NF-κB/COX-2 激活剂佛波酯组(H-THSWD+PMA组),另随机选取等量正常健康 SD 大鼠为 NC 组(常规饲养)、假手术组(sham 组).检测各组大鼠血清凝血、血液流变、炎症因子相关指标水平变化;观察各组大鼠下肢静脉血栓外观并检测湿重;检测各组大鼠下腔静脉血栓及血管内皮细胞凋亡变化情况;检测各组大鼠下腔静脉血栓组织因子(TF)、NF-κB/COX-2 通路相关蛋白表达.结果:与 NC 组、sham 组相比,LEDVT 组大鼠血管内皮细胞损伤,炎性细胞浸润增多,管腔血栓形成,活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)降低,纤维蛋白原(FIB)、血浆粘度、红细胞压积、IL-6、IL-8、IL-1β、血栓湿重、血管内皮细胞凋亡率、TF 平均光密度值、p-NF-κB p65/NF-κB p65、COX-2 表达升高(P<0.05);与 LEDVT 组相比,L-THSWD 组、M-THSWD 组、H-THSWD 组、BAY11-7082 组大鼠血管内皮细胞损伤、炎性细胞浸润以及管腔血栓形成减轻,APTT、TT、PT 升高,FIB、血浆粘度、红细胞压积、IL-6、IL-8、IL-1β、血栓湿重、血管内皮细胞凋亡率、TF 平均光密度值、p-NF-κB p65/NF-κB p65、COX-2 表达减少(P<0.05);与 H-THSWD 组相比,H-THSWD+PMA 组大鼠血管内皮细胞损伤、炎性细胞浸润以及管腔血栓形成加重,APTT、TT、PT 降低,FIB、血浆粘度、红细胞压积、IL-6、IL-8、IL-1β、血栓湿重、血管内皮细胞凋亡率、TF 平均光密度值、p-NF-κB p65/NF-κB p65、COX-2 表达升高(P<0.05).结论:THSWD 可能通过抑制 NF-κB/COX-2 通路,调控炎症与凝血系统动态平衡,进而改善大鼠 LEDVT.
Objective:To explore the effect of Taohong Siwu decoction(THSWD)on lower extremity deep vein thrombosis(LEDVT)in rats via the nuclear factor-kappa B(NF-κB)/cyclooxygenase-2(COX-2)pathway.Methods:The LEDVT rat model was constructed,and successfully modeled rats were randomly separated into LEDVT group,low-dose THSWD group(L-THSWD group),high-dose THSWD group(H-THSWD group),NF-κB inhibitor group(BAY11-7082 group),and high-dose THSWD+NF-κB/COX-2 ac-tivator phorbol 12-myristate 13-acetate group(H-THSWD+PMA group).An equal number of normal healthy SD rats were randomly selected to form the NC group(standard diet)and the sham surgery group(sham group).Changes in serum coagulation,hemorheology,and inflammatory cytokine-related indicators were meas-ured.The appearance of lower limb venous thrombosis in rats was observed,and wet weight was measured.The changes in inferior vena cava thrombosis and endothelial cell apoptosis were measured.The expression of tissue factor(TF)and NF-κB/COX-2 pathway-related proteins in the inferior vena cava thrombosis of rats in each group was detected.Results:Compared with the NC group and the sham group,the LEDVT group showed en-dothelial cell damage,increased inflammatory cell infiltration,luminal thrombosis,decreased activated partial thromboplastin time(APTT),thrombin time(TT),prothrombin time(PT),and increased fibrinogen(FIB),plasma viscosity,hematocrit,IL-6,IL-8,IL-1β,thrombus wet weight,endothelial cell apoptosis rate,TF mean optical density values,p-NF-κB p65/NF-κB p65,and COX-2 expression(P<0.05).Compared with the LEDVT group,the L-THSWD group,H-THSWD group,and BAY11-7082 group showed reduced endothelial cell damage,inflammatory cell infiltration,and luminal thrombus formation in rats,increased APTT,TT,and PT,and reduced FIB,plasma viscosity,hematocrit,IL-6,IL-8,IL-1β,thrombus wet weight,endothelial cell apoptosis rate,TF mean optical density values,p-NF-κB p65/NF-κB p65,and COX-2 expression(P<0.05).Compared with the H-THSWD group,the H-THSWD+PMA group showed increased endothelial cell damage,inflammatory cell infiltration,and luminal thrombus formation in rats,reduced APTT,TT,and PT,and increased FIB,plasma viscosity,hematocrit,IL-6,IL-8,IL-1β,thrombus wet weight,endothelial cell apopto-sis rate,TF mean optical density values,p-NF-κB p65/NF-κB p65,and COX-2 expression(P<0.05).Conclusion:TSD may increase LEDVT in rats by inhibiting the NF-κB/COX-2 pathway and suppressing the inflammatory response.
李攀;田军军
湖北省中医院/湖北中医药大学附属医院普通外科,湖北 武汉 430060湖北省中医院/湖北中医药大学附属医院普通外科,湖北 武汉 430060
下肢深静脉血栓形成核转录因子κB/环氧合酶-2通路桃红四物汤
Lower extremity deep vein thrombosisNuclear factor-kappa B/cyclooxygenase-2 pathwayTaohong siwu decoction
《河北医学》 2026 (4)
586-593,8
湖北省中医药中医药科研联合基金项目,(编号:ZY2025L262)
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