缬草酸调控Sirtuin1/NF-κB通路抑制骨折后深静脉血栓形成  

Valerian acid regulates the Sirtuin1/NF-κB pathway to inhibit postfracture deep vein thrombosis

作　　者：赵瑜潇 胡玉菲 王秀艳[1] 郭建义 ZHAO Yuxiao;HU Yufei;WANG Xiuyan;GUO Jianyi(Department of Clinical Laboratory,The First Affiliated Hospital of Xingtai Medical College/The First Hospital of Xingtai,Xingtai 054001,China)

机构地区：[1]邢台医学高等专科学校第一附属医院/邢台市第一医院检验科,河北邢台054001

出　　处：《生物技术》2023年第6期772-777,共6页Biotechnology

基　　金：邢台市重点研发计划自筹项目(2020ZC175)。

摘　　要：[目的]探究缬草酸对骨折后深静脉血栓形成及Sirtuin1/NF-κB通路的影响。[方法]所有Sprague Dawley大鼠被随机分为3组(每组n=10):假手术组、模型组和缬草酸组。通过HE染色分析下腔静脉组织病理变化。通过蛋白免疫印迹分析Sirtuin1/NF-κB通路的变化。通过酶联免疫吸附剂测定分析炎症因子IL-6、IL-1β和TNF-α的水平。通过全自动凝血分析仪检测凝血酶原时间、活化部分凝血活酶时间、凝血酶时间。[结果]病理分析发现,缬草酸治疗后,模型组大鼠血栓染色变淡,血管再通,血管壁有少数炎症细胞。此外,缬草酸治疗后,模型组大鼠血栓重量逐渐减小(6.36±0.02 vs 11.03±0.02,P<0.05),长度逐渐缩短。此外,模型组大鼠在经过缬草酸治疗后炎症因子水平明显降低(4.67±0.08 vs 7.02±0.01;5.99±0.05 vs 11.02±0.03;5.81±0.06 vs 10.02±0.03;P<0.05),凝血酶原时间、活化部分凝血活酶时间、凝血酶时间水平明显上升。蛋白免疫印迹结果发现,与模型组相比,缬草酸组大鼠的下腔静脉组织中NF-κB p65磷酸化水平降低(0.58±0.02 vs 0.92±0.03;P<0.05),Sirtuin1水平增加(0.69±0.01 vs 0.16±0.03;P<0.05)。[结论]缬草酸能够改善下腔静脉血栓导致的病理损伤、抑制下腔静脉血栓形成,并能抑制血浆中炎症因子的水平。这一作用可能与Sirtuin1表达上调而NF-κB的抑制相关。[Objective]To investigate the effects of valeric acid on deep vein thrombosis(DVT)and Sirtuin1/NF-κB pathway after fracture.[Method]Sprague dawley rats were randomly divided into 3 groups(n=10 each):Sham group,model group and valeric acid group.The pathological changes of inferior vena cava were analyzed by H&E staining.The changes of Sirtuin1/NF-κB pathway were analyzed by Western Blotting.The levels of inflammatory factors IL-6,IL-1βand TNF-αwere analyzed by enzyme-linked immunosorbent assay.Prothrombin time,activated partial thromboplastin time and thrombin time were detected by automatic coagulation analyzer.[Result]Pathological analysis revealed that after valeric acid treatment,thrombus staining became lighter,blood vessels were recanalized,and a few inflammatory cells were found in the vessel wall of the rats in the model group.In addition,after valeric acid treatment,the weight and length of the thrombus in the rats of the model group gradually decreased(6.36±0.02 vs 11.03±0.02,P<0.05).In addition,the levels of inflammatory factors in the model group were significantly decreased after resveratrol treatment(4.67±0.08 vs 7.02±0.01,5.99±0.05 vs 11.02±0.03,5.81±0.06 vs 10.02±0.03,P<0.05),and the levels of prothrombin time,activated partial thromboplastin time,and thrombin time were significantly increased.Western Blot results showed that the phosphorylation level of NF-κB p65 was decreased(0.58±0.02 vs 0.92±0.03,P<0.05)and the level of Sirtuin1 was increased(0.69±0.01 vs 0.16±0.03,P<0.05)in the inferior vena cava tissues of the resveratrol group compared with the model group.[Conclusion]Valeric acid can improve the pathological damage of inferior vena cava thrombosis,inhibit the formation of inferior vena cava thrombosis,and inhibit the levels of inflammatory factors in plasma.This effect may be related to the up-regulation of Sirtuin1 expression and the inhibition of NF-κB.

关 键 词：缬草酸 骨折 深静脉血栓 Sirtuin1 NF-ΚB 炎症 凝血 

分 类 号：R543.6[医药卫生—心血管疾病]