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苍艾挥发油通过调节氧化应激反应对高原心肌肥厚大鼠的治疗作用

Therapeutic Effect of Cang-Ai Volatile Oil on High-Altitude Rats With Cardiac Hypertrophy Through Modulation of Oxidative Stress Response

    摘要
  • 摘要:
    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/L vs. （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。

     

    Abstract:
    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.

     

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