目的 基于7.0T心脏磁共振(cardiac magnetic resonance,CMR)探索苍艾挥发油(Cang-ai volatile oil,CAVO)对青藏高原低压低氧环境心肌肥厚(myocardial hypertrophy,MH)大鼠的治疗作用.方法 将50只雄性SPF级SD大鼠随机分为平原对照组(CON)、低压低氧组(HH)、心肌肥厚模型组(MH)、苍艾治疗组(MH+CAVO)和盐酸贝那普利治疗组(MH+RX),每组10只.除CON组外,将其余组在高原环境(海拔4250 m)自然饲养8周后,给予相应药物灌胃.后采用CMR测量左心室功能及心肌应变.采用HE染色、Masson染色观察心肌间质纤维化情况,小麦胚芽凝集素(wheat germ agglutinin,WGA)染色分析心肌细胞横截面积;透射电镜观察心肌超微结构改变.ELISA法检测血清中心肌肌钙蛋白T(cardiac troponin T,cTnT)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平.结果 相较CON组,MH组的左心室整体周向应变(left ventricular global circumferential strain,LVGCS)[(-18.85±1.67)%]和左心室整体纵向应变(left ventricular global longitudinal strain,LVGLS)[(-20.39±1.48)%]降低(P<0.05).然而,与MH组相 比,MH+CAVO组的LVGCS[(-22.10±1.08)%]和LVGLS[(-24.60±1.72)%]升高(P均<0.05),表明CAVO治疗改善了左心室功能.与CON组比较,MH组血清中GSH-Px[(1173.49±27.10)U/mL vs.(300.83±47.25)U/mL]和SOD水平[(302.27±3.65)U/mL vs.(105.96±4.03)U/mL]降低(P<0.01),MDA水平增加[(6.65±2.99)μmol/Lvs.(57.91±1.13)μmol/L,P<0.01],提示MH组大鼠抗氧化能力下降.经CAVO干预后,MH+CAVO组的大鼠表现出血清中SOD[(278.51±5.97)U/mL]和GSH-Px[(961.82±17.56)U/mL]水平的升高以及MDA[17.79±1.33)μmol/L]水平的降低(P均<0.05).结论 CAVO通过调节氧化应激反应,有效改善高原环境下心肌肥厚大鼠的心功能,同时改善心肌肥厚.
Therapeutic Effect of Cang-Ai Volatile Oil on High-Altitude Rats With Cardiac Hypertrophy Through Modulation of Oxidative Stress Response
Objective To explore the therapeutic effect of Cang-ai volatile oil(CAVO)on rats with myocardial hypertrophy(MH)exposed to the hypobaric hypoxic environment of the Qinghai-Tibet Plateau using 7.0-tesla(7.0T)cardiac magnetic resonance imaging(CMR).Methods A total of 50 male specific pathogen-free(SPF)Sprague-Dawley(SD)rats were randomly assigned to a low-altitude control(CON)group,hypobaric hypoxia(HH)group,myocardial hypertrophy modeling(MH)group,MH modeling plus CAVO treatment(MH+CAVO)group,and MH modeling plus benadryl hydrochloride treatment(MH+RX)group,with 10 rats in each group.Except for the CON group,the rats in all the groups were kept and fed in the standard way for 8 weeks in a high-altitude environment(at 4250 m above sea level),and then given the corresponding treatment drugs by gastric gavage.Afterwards,7.0T high field strength CMR was used to measure left ventricular(LV)function and myocardial strain.Hematoxylin-eosin(HE)staining and Masson staining were performed to observe myocardial interstitial fibrosis.Wheat germ agglutinin(WGA)staining was performed to analyze the cross-sectional area of cardiomyocytes.Transmission electron microscopy was used to observe the ultrastructural changes of the myocardium.Serum levels of cardiac troponin T(cTnT),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-PX)were measured by ELISA.Results Compared with those of the control group,the MH group had significantly lower left ventricular global circumferential strain(LVGCS)at(-18.85±1.67)%and left ventricular global longitudinal strain(LVGLS)at(-20.39±1.48)%(P<0.05).However,the MH+CAVO group had significantly higher LVGCS at(-22.10±1.08)%and LVGLS at(-24.60±1.72)%compared with those of the MH group(both P<0.05),indicating that CAVO treatment improved LV function.The MH group had a decreased level of serum glutathione peroxidase(GSH-Px)in comparison with the CON group([1173.49±27.10]U/mL vs.[300.83±47.25]U/mL,P<0.01),a decreased SOD level in comparison with the CON group([302.27±3.65]U/mL vs.[105.96±4.03]U/mL,P<0.01),and an increased level of serum malondialdehyde(MDA)in comparison with the CON group([57.91±1.13]μmol/L vs.[6.65±2.99]μmol/L,P<0.01),suggesting that the antioxidant capacity of rats in the MH group was decreased.After CAVO intervention,rats in the MH+CAVO group exhibited an increase in the serum levels of SOD at(278.51±5.97)U/mL and GSH-Px at(961.82±17.56)U/mL,as well as a decrease in MDA at(17.79±1.33)μmol/L(all P<0.05).Conclusion CAVO can effectively improve cardiac function in rats with cardiac hypertrophy exposed to high-altitude environment by modulating oxidative stress and ameliorating cardiac hypertrophy.
Cang-ai volatile oil7.0T cardiac magnetic resonanceHigh altitudeHypobaric hypoxiaMyocardial hypertrophy