核因子-κB在深静脉血栓血管内皮细胞中的表达及意义

The expression and significance of NF-κB in endothelial cells of deep venous thrombosis

目的探讨核因子-κB(NF-κB)在孕鼠深静脉血栓形成(DVT)后其血管内皮细胞中的动态变化及意义。方法清洁级SD孕鼠54只,其中48只采用下腔静脉结扎法建立深静脉血栓模型后,随机分为血栓模型组、吡咯烷二硫代氨基甲酸盐(PDTC)干预组,分别于术后6、12、24、72 h处死;余6只为假手术组。比较血栓模型组和PDTC干预组静脉血栓的形成情况并观察其病理学形态,采用免疫组化SP法检测各组血管内皮细胞中NF-κB的表达水平。结果 NF-κB蛋白水平于静脉血栓形成后6 h开始升高,24 h达高峰,72 h后下降。与假手术组比较,血栓模型组和PDTC干预组各时间点静脉血管内皮细胞中NF-κB的表达均显著增强(P<0.05)。NF-κB抑制剂PDTC干预后静脉血管内皮细胞中NF-κB的表达显著下降,72 h后血栓重量与长度比值显著低于血栓模型组(P<0.05)。结论孕鼠DVT血管内皮细胞中NF-κB明显激活,并介导血管内皮的损伤,抑制NF-κB的信号通路可能对DVT有潜在的治疗价值。

Objective To investigate the expression and significance of nuclear factor - KB （ NF -κB） in vascu- lar endothelial cells （VECs） of deep venous thrombosis （DVT） in pregnant rats. Methods Forty - eight Sprague - Daw- ley （SD） pregnant rats were randomly divided into model group and PDTC treated group. DVT model was constructed by inferior vena cava ligation in model and PDTC groups, whereas 6 SD pregnant rats were included as sham - operation group. The subjects were sacrificed 6, 12, 24 and 72 h after operation （n =6 each）. The thrombus formation and patho- logical changes were observed under the optical microscope. The protein level of NF - κB in VECs of DVT was assessed by SP immunohistochemical method. Results Since the 6th hour, the expression of NF - κB protein was elevated and reached a peak at 8th hour then was stayed at the plateau until decreased at 72nd hour in DVT models. The level of NF - κB in VECs in the model and the PDTC treated groups were significantly higher than that in the sham - operated group （P〈0.05）. Furthermore, significant reduction of NF- κB in VECs, and the weight and length of DVT at 72nd hour were revealed in PDTC treated subjects when comparing with those in model group （P 〈 0. 05）. Conclusion The activated NF - κB in VECs mediates vessel wall damage, suggesting the potential therapeutic significance of NF - κB inhibitor for DVT disease.