摘要
目的利用心脏磁共振(cardiac magnetic resonance,CMR)组织追踪技术评估高原低氧环境下亚硒酸钠(sodium selenite,SE)对肺动脉高压(pulmonary arterial hypertension,PAH)后左心室功能的改善作用并初步探索SE提升PAH后左心室功能的潜在机制。材料与方法46只雄性SD大鼠于购置第二日从成都(海拔500 m)陆运至青海省玉树藏族自治州高原动物实验室(海拔4250 m),随机分为对照组(n=10)、模型组[野百合碱(monocrotaline,MCT)组,n=20]和治疗组(SE组,n=16)。高原低氧环境下饲养28周后,MCT组和SE组大鼠均接受一次性腹腔注射60 mg/kg的MCT以建立PAH模型,而对照组则接受等量的生理盐水注射。一周后,SE组大鼠通过灌胃方式给予0.7 mg/kg的SE持续治疗一个月,对照组和MCT组进行常规饲养。干预完成后将大鼠运回成都。随机从三组中各选取8只大鼠进行CMR成像,以评估左心室功能、应变和T2弛豫时间。CMR扫描结束后取材大鼠心脏组织和血液分别进行病理、血生化检测。结果相较于对照组,MCT组的左心室射血分数(left ventricular ejection fraction,LVEF)(61.36%±4.50%)和左心室整体周向应变(left ventricular global circumferential strain,LVGCS)(−19.81%±0.84%)显著降低(P值均<0.05)。然而,与MCT组相比,SE组的LVEF(75.29%±5.67%)、左心室整体径向应变(left ventricular global radial strain,LVGRS)(42.90%±5.94%)和LVGCS(−21.43%±1.33%)明显提高(P值均<0.05),表明SE治疗提高了PAH后左心室功能。对照组和MCT组血清中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的含量差异具有统计学意义[对照组vs.MCT组:(16544.38±3734.02)U/mL vs.(9974.00±900.80)U/mL,P<0.05],MCT组血清中丙二醛(malondialdehyde,MDA)相较于对照组有所增加[MCT组vs.对照组:9.00(7.60,13.20)μmol/L vs.3.86(3.60,6.20)μmol/L,P<0.01],提示MCT组大鼠抗氧化能力下降。经SE干预后,SE组的大鼠表现出血清中超氧化物歧化酶(superoxide dismutase,SOD)(292.60±44.38)U/mL和GSH-Px(17843.26±3585.44)U/mL水平的升高以及MDA[5.37(5.10,6.20)μmol/L]水平的降低(P值均<0.05)。凋亡染色表明,与对照组相比,MCT组左心室的相对荧光强度显著增高(P<0.001),而治疗后SE组的相对荧光强度较MCT组明显降低(P<0.001)。结论CMR组织追踪技术能够定量评估肺动脉高压后左心室功能的异常;SE在高原低氧环境下能改善PAH后左心室功能,其机制可能与其提高大鼠抗氧化能力、减轻心肌细胞凋亡有关。
Objective:To assess the improvement of sodium selenite(SE)on left ventricular function after pulmonary arterial hypertension(PAH)in a high-altitude hypoxic environment using cardiac magnetic resonance tissue tracking(CMR-TT).At the same time,the potential mechanism of SE improving left ventricular function after PAH was preliminarily explored.Materials and Methods:Forty-six male SD rats were relocated overland from Chengdu(altitude 500 m)to the Plateau Animal Laboratory in Yushu Tibetan Autonomous Prefecture,Qinghai Province(altitude 4250 m)the day following their acquisition.Subsequently,they were randomly assigned to one of three groups:a control group(n=10),a model group treated with monocrotaline(MCT)(MCT group,n=20),and a treatment group(SE group,n=16).After being raised in a hypoxic environment for 28 weeks,both the MCT and SE groups of rats were administered a one-time intraperitoneal injection of 60 mg/kg MCT to establish the PAH model,whereas the control group received an equivalent volume of saline injection.One week later,rats in the SE group were treated with 0.7 mg/kg of SE via oral gavage for a continuous period of one month,while the control group and MCT group were kept on routine feeding.Upon completion of the intervention,the rats were transported back to Chengdu where 8 rats from each of the three groups were randomly selected for CMR imaging to assess left ventricular function,strain,and T2 relaxation time.After completing the CMR scan,heart tissue and blood samples are collected from the rat for respective pathological and biochemical analysis.Results:Compared with control group,MCT group of left ventricular ejection fraction(LVEF)(61.36%±4.50%)and left ventricular global circumferential strain(LVGCS)(−19.81%±0.84%)were significantly decreased(all P<0.05).However,LVEF(75.29%±5.67%),left ventricular global radial strain(LVGRS)(42.90%±5.94%),and LVGCS(−21.43%±1.33%)were significantly higher in the SE group compared with the MCT group(all P<0.05).The results showed that SE treatment improved left ventricular function after PAH.The levels of serum glutathione peroxidase(GSH-Px)in the control and MCT groups were statistically significant[control group vs.MCT group:(16544.38±3734.02)U/mL vs.(9974.00±900.80)U/mL,P<0.05],serum malondialdehyde(MDA)increased in MCT group compared to control group[MCT group vs.control group:9.00(7.60,13.20)μmol/L vs.3.86(3.60,6.20)μmol/L,P<0.01],suggesting that the antioxidant capacity of rats in MCT group decreased.After SE intervention,rats in the SE group exhibited increased serum levels of superoxide dismutase(SOD)(292.60±44.38)U/mL and GSH-Px(17843.26±3585.44)U/mL as well as decreased MDA levels[5.37(5.10,6.20)μmol/L](all P<0.05).The apoptosis staining showed that the relative fluorescence intensity of the left ventricle of MCT was significantly higher compared with that of control group(P<0.001),whereas SE treatment resulted in a significant decrease in the relative fluorescence intensity of apoptosis staining in the SE group compared with that of the MCT group(P<0.001).Conclusions:The CMR-TT technique enables the quantitative evaluation of left ventricular functional abnormalities following pulmonary arterial hypertension.SE can improve left ventricular function after PAH in hypoxic environment,which may be related to increasing antioxidant capacity and alleviating left ventricular cardiomyocyte apoptosis.
作者
尹红科
梁博深
陈皓田
王磊
赵思斯
方鑫
郜发宝
YIN Hongke;LIANG Boshen;CHEN Haotian;WANG Lei;ZHAO Sisi;FANG Xin;GAO Fabao(Department of Radiology,West China Hospital,Sichuan University,Chengdu 610041,China;Molecular Imaging Center,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《磁共振成像》
CAS
CSCD
北大核心
2024年第4期126-132,共7页
Chinese Journal of Magnetic Resonance Imaging
基金
国家自然科学基金项目(编号:81930046)。
关键词
肺动脉高压
左心室心功能
高原低氧环境
亚硒酸钠
大鼠
磁共振成像
pulmonary arterial hypertension
left ventricular cardiac function
high-altitude hypoxic environment
sodium selenite
rat
magnetic resonance imaging
作者简介
通信作者:郜发宝,E-mail:gaofabao@wchscu.cn。
