黄芩苷对血栓栓塞致急性肺栓塞大鼠NF-κB信号通路抑制作用的实验研究  

Inhibition Effect of Baicalin on NF-κB Signal Pathway in Acute Pulmonary Embolism Rats Induced by Thromboembolism

作　　者：蔡娟娟 黄静[2] 苏玲玲[2] 徐俪颖 CAI Juanjuan;HUANG Jing;SU Lingling;XU Liying(Zhejiang Chinese Medicine University,Hangzhou,Zhejiang 310000;The Affiliated Hospital of Medical School,Ningbo University,Ningbo,Zhejiang 315300;The First Affiliated Hospital of Zhejiang Chinese Medicine University,Hangzhou.Zhejiang,310006)

机构地区：[1]浙江中医药大学,浙江杭州310000 [2]宁波大学医学院附属医院,浙江宁波315300 [3]浙江中医药大学附属第一医院,浙江杭州310006

出　　处：《中国中医药科技》2022年第3期378-383,共6页Chinese Journal of Traditional Medical Science and Technology

基　　金：浙江省中医药科技计划项目(2020ZB067)。

摘　　要：目的:研究黄芩苷对血栓栓塞致急性肺栓塞(acute pulmonary embolism,APE)大鼠NF-κB信号通路的调控作用。方法:选取60只雄性SD大鼠随机分为Sham组、APE组、APE+黄芩苷低剂量组(1 m L/kg)、APE+黄芩苷中剂量组(2 m L/kg)、APE+黄芩苷高剂量组(4 m L/kg)。除Sham组外,其余组大鼠均使用自体血栓造模建立APE动物模型,术后4 h麻醉大鼠,对各组大鼠行肺动脉压(m PAP)、右心室压力(RVP)检测、血气分析、肺脏病理、肺湿干重比(Wet/Dry ratio)及氧化应激指标检测,Western blot检测核因子-κB亚基p65亲和肽(NF-κBp65)、磷酸化核因子-κB亚基p65亲和肽(p-NF-κBp65)、核因子κB抑制剂(κ-Bα)、磷酸化核因子κB抑制剂(p-IκBα)等蛋白表达水平。结果:相较Sham组,APE组m PAP、RVP、Wet/Dry ratio、髓过氧化物(MPO)活性、MDA含量、NF-κBp65、p-NF-κBp65蛋白表达水平明显升高(P<0.01),PaO_(2)、SOD活性、p-IκBα蛋白表达明显下降(P<0.01);与APE组相比,APE+黄芩苷中剂量组RVP、MPO活性、MDA含量、p-NF-κBp65蛋白表达水平下调(P<0.05),PaO_(2)、p-IκBα蛋白表达水平上调(P<0.05),APE+黄芩苷高剂量组m PAP、RVP、Wet/Dry ratio、MPO活性、MDA含量、p-NF-κBp65蛋白表达水平显著降低(P<0.05或P<0.01),PaO_(2)、SOD活性、p-IκBα蛋白表达水平上升(P<0.05或P<0.01)。肺组织HE染色结果显示,与Sham组相比,APE组可见肺组织呈一定病理学损伤,肺细胞形态呈不规则状,肺泡内和间质水肿、出血以及伴有炎症细胞浸润,而黄芩苷处理组的大鼠肺组织与APE组相比,肺组织病理性损伤程度有所改善。结论:黄芩苷通过抑制NF-κB信号通路,上调p-IκBα蛋白表达水平,下调p-NF-κBp65蛋白表达,剂量依赖性改善APE大鼠的m PAP、RVP水平,提高PaO_(2),改善肺组织损伤程度,调高机体抗氧化抗炎能力,对受损肺组织起到保护作用。Objective:To study the regulatory effect of Baicalin on APE rats by inhibiting NF-κB signal pathway.Methods:Sixty male SD rats were randomly divided into Sham group,APE group,APE+Baicalin low-dose group(1 mL/kg),APE+Baicalin medium-dose group(2 mL/kg),APE+Baicalin high-dose group(4 mL/kg).Except Sham group,APE animal model was established by autothrombus modeling in other groups.The rats were anesthetized 4 h after surgery,and pulmonary artery pressure(mPAP),right ventricular pressure(RVP),blood gas analysis,lung pathology,Wet/Dry ratio of lung and oxidative stress indexes were detected.The protein expression levels of nuclear factor-κB subunit P65 affinity peptide(NF-κBp65),phosphorylated nuclear factor-κB subunit P65 affinity peptide(P-NF-κBp65),nuclear factorκB inhibitor(κ-Bα)and phosphorylated nuclear factorκB inhibitor(P-IκBα)were detected by Western blot.Results:Compared with Sham group,mPAP,RVP,Wet/Dry ratio,myeloperoxide(MPO)activity,MDA content,NF-κBp65 and P-NF-κBp65 protein expression levels in APE group were significantly increased(P<0.01).The levels of PaO_(2),SOD and protein expression of P-IκBαdecreased significantly(P<0.01).Compared with APE group,RVP and MPO activities,MDA content and protein expression level of P-NF-κBp65 in APE+baicalin medium-dose group were down-regulated(P<0.05),while protein expression level of PaO_(2)and P-IκBαwas up-regulated(P<0.05).MPAP,RVP,Wet/Dry ratio,MPO activity,MDA content and p-NF-κBp65 protein expression level in APE+Baicalin high-dose group were significantly decreased(P<0.05 or P<0.01).The levels of PaO_(2),SOD and protein expression of P-IκBαincreased(P<0.05 or P<0.01).HE staining results of lung tissue showed that compared with Sham group,pathological injury of lung tissue was observed in APE group,lung cell morphology was irregular,alveolar and interstitial edema,hemorrhage and inflammatory cell infiltration were observed,while pathological injury degree of lung tissue in Baicalin treated group was improved compared with APE group.Concl

关 键 词：黄芩苷 急性肺栓塞 NF-ΚB信号通路 血栓栓塞 

分 类 号：R285.5[医药卫生—中药学]