水仙环素对低氧性肺动脉高压大鼠右心室重塑的影响及机制  

Effects and mechanism of narciclasine on right ventricular remodeling in hypoxia-induced pulmonary hypertension rats

作　　者：张婧 卫玮[2] 韦红梅[1] 薛茜茜 金玲 张楠 吴宾 ZHANG Jing;WEI Wei;WEI Hongmei;XUE Xixi;JIN Ling;ZHANG Nan;WU Bin(Department of Nutrition,Xinjiang Military General Hospital,Urumqi 830000,China;不详)

机构地区：[1]新疆军区总医院营养科,新疆乌鲁木齐830000 [2]新疆军区总医院检验科,新疆乌鲁木齐830000 [3]新疆军区总医院老年医学科,新疆乌鲁木齐830000 [4]新疆军区总医院皮肤科,新疆乌鲁木齐830000

出　　处：《陕西医学杂志》2023年第7期793-797,共5页Shaanxi Medical Journal

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C644);新疆军区总医院喀喇昆仑基金资助项目(2022JC002)。

摘　　要：目的:探讨水仙环素(Nar)对低氧性肺动脉高压(HPH)大鼠右心室重塑的影响及可能机制。方法:将SD大鼠随机分为对照组(NC组)、对照+Nar组(NC+Nar组)、HPH组、HPH+Nar组(HPH+Nar组)。HPH组和HPH+Nar组置于低压低氧人工实验舱内维持6周,NC组和NC+Nar组置于常压常氧环境中维持6周。从第5周开始,NC+Nar组和HPH+Nar组给予Nar[0.1 mg/(kg·d)]灌胃维持2周,NC组和HPH组给予同等体积的0.9%氯化钠溶液灌胃维持2周。检测大鼠右室血流动力学、右室重塑指标、血管活性物质水平以及肺组织核因子κB/p65(NF-κB/p65)、肌肉环指蛋白1(MuRF1)和大电导钙激活钾通道β1亚基(BK-β1)蛋白表达。结果:与NC组和NC+Nar组相比,HPH组平均肺动脉压(mPAP)、右心室收缩压(RVSP)、右室压力最大上升/下降速率(±dp/dt_(max))均显著增加(均P<0.05),内皮素-1(ET-1)和脑钠肽(BNP)显著增加(均P<0.05),一氧化氮(NO)、总一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)显著降低(均P<0.05),右心室肥厚指数(RVHI)、右心室重量/体重(RV/BW)、右室胶原容积分数(CVF)显著增加(均P<0.05),p65和MuRF1表达显著增加(均P<0.05),BK-β1表达显著降低(均P<0.05)。与HPH组相比,HPH+Nar组mPAP、RVSP、±dp/dt_(max)显著降低(均P<0.05),ET-1和BNP显著降低(均P<0.05),NO、总NOS和iNOS显著增加(均P<0.05),RVHI、RV/BW、右室CVF显著降低(均P<0.05),p65和MuRF1表达显著降低(均P<0.05),BK-β1表达显著增加(均P<0.05)。结论:水仙环素可改善低氧性肺动脉高压大鼠右心室重塑,其机制可能与抑制肺动脉平滑肌中NF-κB/MuRF1信号通路介导的BK-β1降解有关。Objective:To explore the effects of narciclasine(Nar)on right ventricular remodeling in hypoxia-induced pulmonary hypertension(HPH)rats and potential mechanisms.Methods:Sprague-dawley(SD)rats were randomly divided into NC group,NC+Nar group,HPH group and HPH+Nar group.HPH group and HPH+Nar group were placed in low-pressure and low-oxygen artificial experimental chamber,and NC group and NC+Nar group were placed in atmospheric oxygen SPF environment for 6 weeks.From the fifth week,The NC+Nar and HPH+Nar groups were given a dose of 0.1 mg/(kg·d)Nar,while the NC group and HPH group were intragastrically given equivalent volumes of distilled water for 2 weeks.Right ventricular hemodynamics,right ventricular remodeling indicators,vasoactive substances and the expressions f NF-κB/p65,MuRF1 and BK-β1 protein in lung tissue were detected.Results:Compared with NC group and NC+Nar group,the HPH group had significant increases in mPAP,RVSP,±dp/dt_(max),ET-1,BNP,RVHI,RV/BW,CVF,p65 and MuRF1,and had significant decreases in NO,NOS,iNOS,BK-β1(all P<0.05).Compared with HPH group,mPAP,RVSP,±dp/dt_(max),ET-1,BNP,RVHI,RV/BW,CVF,p65 and MuRF1 decreased significantly,and NO,t-NOS,iNOS and BK-β1 increased significantly in HPH+Nar group(all P<0.05).Conclusion:Narcicycline can improve right ventricular remodeling in rats with hypoxia-induced pulmonary hypertension possibly by inhibiting NF-κB/MuRF1 signaling pathway mediated BK-β1 degradation in pulmonary artery smooth muscle.

关 键 词：水仙环素 低氧性肺动脉高压 心室重塑 大电导钙激活钾通道 肌肉环指蛋白1 核因子κB 

分 类 号：R541.3[医药卫生—心血管疾病]