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益气温阳活血汤通过ERK/Nrf2信号通路改善慢性心力衰竭大鼠的氧化应激损伤

Yiqi Wenyang Huoxue Decoction ameliorates oxidative stress injury in rats with chronic heart failure via the ERK/Nrf2 signaling pathway

    摘要
  • 摘要:
    目的 探讨益气温阳活血汤对慢性心力衰竭(CHF)大鼠氧化应激损伤的影响及机制。
    方法 采用腹主动脉缩窄法建立CHF大鼠模型。将大鼠分为假手术组(n=10)、CHF组(n=10)、益气温阳活血汤低剂量组(n=10)、益气温阳活血汤中剂量组(n=10)、益气温阳活血汤高剂量组(n=10)。测量各组心脏结构和功能参数, 包括左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左室短轴缩短率(LVFS)和左室射血分数(LVEF)。检测各组氧化应激指标，包括谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)和过氧化氢酶(CAT)。评估各组心脏损伤标志物，包括肌酸激酶-MB (CK-MB)和乳酸脱氢酶(LDH)。采用苏木精-伊红染色和Masson染色观察心肌细胞形态和心肌纤维化。采用TUNEL染色观察心肌细胞凋亡。采用蛋白质印迹法分析ERK/Nrf2信号通路相关蛋白的表达。
    结果 CHF组的LVESD和LVEDD大于假手术组, LVEF和LVFS低于假手术组，差异有统计学意义(P < 0.05)。益气温阳活血汤低剂量组、益气温阳活血汤中剂量组、益气温阳活血汤高剂量组的LVESD和LVEDD小于CHF组, LVEF和LVFS高于CHF组，差异有统计学意义(P < 0.05)。CHF组血清SOD、GSH-Px、CAT水平低于假手术组, MDA水平高于假手术组，差异有统计学意义(P < 0.05)。益气温阳活血汤低剂量组、益气温阳活血汤中剂量组、益气温阳活血汤高剂量组的SOD、GSH-Px和CAT水平高于CHF组, MDA水平低于CHF组，差异有统计学意义(P < 0.05)。CHF组血清CK-MB、LDH水平高于假手术组，差异有统计学意义(P < 0.05)。益气温阳活血汤低剂量组、益气温阳活血汤中剂量组、益气温阳活血汤高剂量组的CK-MB、LDH水平低于CHF组，差异有统计学意义(P < 0.05)。益气温阳活血汤治疗组显著抑制了心肌细胞的凋亡，改善了心肌细胞形态，并减少了心肌纤维化。蛋白质印迹法分析显示，益气温阳活血汤显著上调了ERK蛋白的磷酸化水平和Nrf2的表达。
    结论 益气温阳活血汤可能通过ERK/Nrf2信号通路减轻CHF大鼠模型的氧化应激损伤。

     

    Abstract:
    Objective To investigate the effects and mechanisms of Yiqi Wenyang Huoxue Decoction on oxidative stress injury in rats with chronic heart failure (CHF).
    Methods A CHF rat model was established using the abdominal aortic constriction method. The rats were divided into sham-operated group (n=10), CHF group (n=10), low-dose Yiqi Wenyang Huoxue Decoction group (n=10), medium-dose Yiqi Wenyang Huoxue Decoction group (n=10) and high-dose Yiqi Wenyang Huoxue Decoction group (n=10). Cardiac structure and functional parameters were measured in each group, including left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Oxidative stress indicators were detected in each group, including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT). Cardiac injury markers were evaluated in each group, including creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Hematoxylin-eosin staining and Masson staining were used to observe cardiomyocyte morphology and myocardial fibrosis. TUNEL staining was employed to observe cardiomyocyte apoptosis. Western blotting was utilized to analyze the expression of proteins related to the ERK/Nrf2 signaling pathway.
    Results The LVESD and LVEDD in the CHF group were significantly larger than those in the sham-operated group, while LVEF and LVFS were significantly lower (P < 0.05). The LVESD and LVEDD in the low-dose, medium-dose and high-dose Yiqi Wenyang Huoxue Decoction groups were significantly smaller than those in the CHF group, while LVEF and LVFS were significantly higher (P < 0.05). The serum levels of SOD, GSH-Px and CAT in the CHF group were significantly lower than those in the sham-operated group, while the MDA level was significantly higher (P < 0.05). The SOD, GSH-Px and CAT levels in the low-dose, medium-dose and high-dose Yiqi Wenyang Huoxue Decoction groups were significantly higher than those in the CHF group, while the MDA level was significantly lower (P < 0.05). The serum levels of CK-MB, and LDH in the CHF group were significantly higher than those in the sham-operated group (P < 0.05). The CK-MB, and LDH levels in the low-dose, medium-dose and high-dose Yiqi Wenyang Huoxue Decoction groups were significantly lower than those in the CHF group (P < 0.05). The treatment groups with Yiqi Wenyang Huoxue Decoction significantly inhibited cardiomyocyte apoptosis, improved cardiomyocyte morphology, and reduced myocardial fibrosis. Western blotting analysis revealed that Yiqi Wenyang Huoxue Decoction significantly upregulated the phosphorylation level of ERK protein and the expression of Nrf2.
    Conclusion Yiqi Wenyang Huoxue Decoction may alleviate oxidative stress injury in a rat model of CHF via the ERK/Nrf2 signaling pathway.

     

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