氧化苦参碱通过调控RhoA/ROCK1/COX2/PGIS信号通路抑制野百合碱诱导的大鼠右心室心肌肥厚的作用  

The Effect of Oxymatrine on Monocrotaline-induced Right Ventricular Hypertrophy via Repressing RhoA/ROCK1 Mediated COX2/PGIS Pathway

作　　者：李本鹏[1] 徐玉平[1] 韦朝倩 李枝吉 戴贵东 Li Benpeng;Xu Yuping;Wei Chaoqian;Li Zhiji;Dai Guidong(Kaili University,Kaili 556011,China)

机构地区：[1]凯里学院,凯里556011

出　　处：《世界科学技术-中医药现代化》2022年第10期4031-4037,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：贵州省科学技术厅一般项目(黔科合LH字[2016]7324号):氧化苦参碱调控Akt/GSK3β通路抑制大鼠右心衰竭的研究,负责人:李本鹏;国家自然科学基金委员会地区项目(81860659):氧化苦参碱舒张肺动脉抑制肺动脉高压的机制及其联合用药研究,负责人:戴贵东;黔东南苗族侗族自治州科技局重点项目(黔东南财教[2022]51klxy23):黔东南州2022年扶持市(州)高校质量提升工程项目专项,负责人:王翔。

摘　　要：目的本文探讨氧化苦参碱通过调控RhoA/ROCK/COX/PGIS信号通路对野百合碱致肺动脉高压大鼠右心室心肌肥厚抑制作用。方法将50只雄性大鼠随机分为正常对照组、野百合碱组、氧化苦参碱组(25、50、100 mg·kg^(-1))。野百合碱组及各用药组单次皮下注射野百合碱(60 mg·kg^(-1)),正常对照组给予等量的生理盐水,氧化苦参碱灌胃给药均在皮下注射野百合碱1 h后。4周后,分离大鼠右心室(RV)、左心室+室间隔(LV+S)并称重,计算RV/(LV+S)的比值;HE染色观察心肌病理变化;Western blot检测右心室组织中RhoA、ROCK1、ROCK2、COX1、COX2、PGIS蛋白的表达。结果与正常组比较,野百合碱组大鼠终末体重显著降低,大鼠心脏肥厚指数显著增加;与野百合碱组相比,氧化苦参碱给药4周后能明显减小RV/(LV+S)的比值,增加终末体重,改善右心室病理变化,明显降低右心室组织中RhoA、ROCK1、COX2、PGIS的表达水平。结论氧化苦参能够抑制野百合碱诱导的肺动脉高压大鼠右心室重构,其机制与抑制RohA/ROCK1/COX2/PGIS通路有关。Objective To investigate oxymatrine on Monocrotaline(MCT)induced pulmonary arterial hypertension(PAH)rats via inhibiting RohA/ROCK/COX/PGIS signaling pathway and effect on right ventricular hypertrophy.Methods SD rats were randomly divided into control group,MCT group,oxymatrine group(25,50,100 mg·kg^(-1)),with 10 rats in each group.The pulmonary hypertension rat model was established by a single subcutaneous injection of MCT(60 mg·kg^(-1))into the back of the rats.Control group was injected with the same amount of physiological saline.Oxymatrine group was gavage with oxymatrine intragastrically administered,while MCT group and control group were given the same amount of physiological saline.Oxymatrine was administered by gavage 1 h after subcutaneous injection of monocrotaline.The drug was administered continuously for 4 weeks.Right ventricular hypertrophy index(RVHI),right ventricular was observed by hematoxylin-eosin(HE)staining.Western blot was utilized to determine RhoA,ROCK1,ROCK2,COX1,COX2 and PGIS protein expression in the Right Ventricular tissues.Results Compared with the normal group,the MCT group rat`s body weight was significantly decreased,while its RVHI were markedly increased.Compared with the MCT group,Oxymatrine rat’s body weight was significantly increased,while its RVHI were markedly decreased,and improved the pathological changes of right ventricle,meanwhile reduced the expression of protein RhoA,ROCK1,COX2,PGIS.Conclusion Oxymatrine can inhibit ventricular remodeling in rats with pulmonary hypertension,which may be related to the inhibition of RhoA/ROCK1 and COX2/PGIS signaling pathway.

关 键 词：氧化苦参碱 心肌肥厚 野百合碱 RohA/ROCK通路 COX2/PGIS通路 

分 类 号：R285.5[医药卫生—中药学]