摘要
【目的】探讨柚皮素抗大鼠下肢深静脉血栓形成机制。【方法】将60只大鼠随机分为6组,即假手术组,模型组,柚皮素低、中、高剂量组和柚皮素高剂量+STING激动剂2.5己酮可可碱(DMXAA)组,每组10只。检测各组大鼠凝血指标[D-二聚体(D-dimer)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)],炎症指标[白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)]及氧化应激指标[丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)];苏木素-伊红(HE)染色法检测静脉血栓形成;检测血栓湿质量和干质量;透射电镜检测静脉血栓超微结构;Western Blot法检测静脉血栓组织中环鸟苷酸-腺苷酸合成酶(c GAS)、干扰素基因刺激因子(STING)蛋白表达。【结果】(1)与假手术组比较,模型组大鼠D-dimer水平,IL-1β、IL-6、TNF-α水平,MDA含量,血栓湿质量和干质量增加,TT、APTT、PT,SOD活性和GSH-Px活性降低(均P<0.05);与模型组比较,柚皮素低、中、高剂量组大鼠D-dimer水平,IL-1β、IL-6、TNF-α水平,MDA含量,血栓湿质量和干质量降低,TT、APTT、PT,SOD活性和GSH-Px活性增加(均P<0.05),且呈剂量依赖性;与柚皮素高剂量组比较,柚皮素高剂量+DMXAA组大鼠D-dimer水平,IL-1β、IL-6、TNF-α水平,MDA含量,血栓湿质量和干质量升高,TT、APTT、PT,SOD活性和GSH-Px活性降低(均P<0.05)。(2)与假手术组比较,模型组大鼠静脉血栓组织中cGAS、STING蛋白表达水平升高(P<0.05);与模型组比较,柚皮素低、中、高剂量组大鼠静脉血栓组织中cGAS、STING蛋白表达水平均显著降低(P<0.05);柚皮素高剂量+DMXAA组大鼠cGAS、STING蛋白表达水平显著高于柚皮素高剂量组(P<0.05)。【结论】柚皮素可通过抑制cGAS/STING信号通路活化,抑制炎症、氧化应激反应,从而缓解下肢深静脉血栓形成。
Objective To investigate the mechanism of naringenin resisting lower extremity deep venous thrombosis(LEDVT)in rats.Methods Sixty rats were randomly divided into 6 groups,i.e.,sham-operation group,model group,naringenin low-,medium-,and high-dose groups,and naringenin high-dose+STING agonist 2.5 hexamethylene cacodylate(DMXAA)group,with 10 rats in each group.The coagulation indexes[D-dimer,thrombin time(TT),activated partial thromboplastin time(APTT),prothrombin time(PT)],inflammation indexes[interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factorα(TNF-α)]and oxidative stress indexes[malondialdehyde(MDA),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)];Hematoxylineosin(HE)staining to detect thrombus formation in venous tissues;wet and dry mass of thrombus were detected;ultrastructure of venous thrombus was detected by transmission electron microscope(TEM);protein expressions of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)in venous thrombus tissue were detected by Western Blot.Results(1)Compared with the sham-operation group,rats in the model group showed an increase in D-dimer levels,IL-1β,IL-6,TNF-αlevels,MDA content,thrombus wet and dry mass,and a decrease in TT,APTT,PT,SOD activity,and GSH-Px activity(all P<0.05);and compared with the modelgroup,rats in naringen’s low-,medium-,and high-dose groups showed a decrease in D-dimer levels,IL-1β,IL-6,TNF-α levels,MDA content,thrombus wet and dry mass,TT,APTT and PT,SOD activity and GSHPxactivity were increased(P<0.05)in a dose-dependent manner compared with the model group;compared withthe naringenin high-dose group,rats in the naringenin high-dose + DMXAA group,D-dimer levels,IL-1β,IL-6, TNF-α levels, MDA content, thrombus wet and dry mass were elevated, TT, APTT and PT, SODactivity and GSH- Px activity were decreased(P<0.05).(2)Compared with the sham- operation group, theexpression levels of cGAS and STING proteins in the venous thrombus tissues of rats in the model group wereelevated(P<0.05);compared with the
作者
张玉莲
谢华
ZHANG Yu-Lian;XIE Hua(Chongqing University Three Gorges Hospital,Chongqing 404000,China)
出处
《广州中医药大学学报》
CAS
2024年第1期192-199,共8页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
重庆市科卫联合中医药科技项目(编号:ZY201802109)。
