活血通脉方对慢性心力衰竭大鼠心肌纤维化和心肌细胞能量代谢的影响研究
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R285.5

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国家自然科学基金面上项目(71973094);湖州市科学技术局项目(2018GYB43)


A Study on Effect of Huoxue Tongmai Prescription on Myocardial Fibrosis and Myocardial Cell Energy Metabolism in Rats with Chronic Heart Failure
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    摘要:

    目的:探讨活血通脉方对慢性心力衰竭 (CHF) 大鼠心肌纤维化 (MF) 和心肌细胞能量代谢的影响。方法:将60 只 SD 大鼠随机选择 10 只作为假手术组,其余大鼠用腹主动脉缩窄法建立 CHF 模型。模型制备成功的 50 只大鼠随机分为模型组、阳性对照组及活血通脉方高、中、低剂量组(高、中、低剂量组),每组 10 只。阳性对照组按 1.5 mg/kg 的剂量灌胃赖诺普利;高、中、低剂量组按 16.0、8.0、4.0 g/kg 的剂量灌胃活血通脉方;假手术组与模型组大鼠灌胃等容积的生理盐水。每天1 次,持续 4 周。计算各组大鼠心质量指数,检测左室射血分数(LVEF)、左心室短轴收缩率(LVFS)及心肌组织转化生长因子-β1 (TGF-β1)、基质金属蛋白酶-9(MMP-9)水平、5'-单磷酸腺苷(AMP)依赖的蛋白激酶(AMPK)、过氧化物酶体增殖剂激活受体 γ (PPARγ)、辅助激活因子-1α (PGC-1α) 蛋白及 mRNA 表达水平。结果:与假手术组比较,模型组 LVEF、LVFS、AMPK、PGC-1α 蛋白及 mRNA 相对表达下降 (P<0.05),心质量指数及 TGF-β1、MMP-9 水平升高 (P<0.05)。与模型组比较,活血通脉方高、中、低剂量组和阳性对照组 LVEF、LVFS 及 AMPK、PGC-1α 蛋白与 mRNA 相对表达升高(P<0.05),心质 量指数及 TGF-β1、MMP-9 水平降低(P<0.05)。与阳性对照组比较,活血通脉方中、低剂量组LVEF、LVFS、AMPK、PGC-1α蛋白及 mRNA 相对表达较低 (P<0.05),心质量指数及 TGF-β1、MMP-9 水平较高 (P<0.05)。结论:活血通脉方能显著提高CHF 大鼠心功能,改善大鼠心肌纤维化,提高心肌细胞能量代谢,其机制可能与上调 AMPK、PGC-1α 表达,下调 TGF-β1、MMP-9 水平有关。

    Abstract:

    Abstract:Objective:To investigate the effect of Huoxue Tongmai prescription on myocardial fibrosis(MF) and myocardial cell energy metabolism in rats with chronic heart failure(CHF). Methods:A total of 60 SD rats were randomly selected;10 rats were taken as the sham operation group,and the other 50 rats were used to establish CHF models by abdominal aortic coarctation. After successful establishment,the 50 rats were randomly divided into the model group,the positive control group and the Huoxue Tongmai prescription group with high,medium and low dose respectively(the high,medium and low dose groups),with 10 rats in each group. The positive control group was given a dose of 1.5 mg/kg of lisinopril by gavage; the high, medium and low dose groups were given a dose of 16.0, 8.0 and 4.0 g/kg of Huoxue Tongmai prescription respectively by gavage;the sham operation group and the model group were given equal volume of normal saline by gavage. All the groups were given gastric perfusion once a day for four weeks. The heart weight indexes of rats in each group were calculated;the levels of the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS)、transforming growth factor β1(TGF-β1),matrix metalloproteinase-9(MMP-9),the expression levels of protein kinase(AMPK) depended on 5'- adenosine monophosphate(AMP) and peroxisome proliferator activated receptors γ(PPARγ) coactivator-1α(PGC-1α) protein and mRNA of myocardial tissue were detected. Results:Compared with those in the sham operation group,LVEF, LVFS and the relative expressions of AMPK,PGC-1α protein and mRNA in the model group were decreased(P<0.05);heart weight index and the levels of TGF- β1 and MMP-9 were increased(P<0.05). Compared with those in the model group, LVEF,LVFS,and the relative expressions of AMPK,PGC-1α protein and mRNA were increased in the high,medium and low dose groups and the positive control group(P<0.05);heart weight indexes and the levels of TGF-β1 and MMP-9 were decreased(P<0.05). Compared with those in the positive control group,LVEF,LVFS and the relative expressions of AMPK, PGC-1α protein and mRNA in the medium and low dose groups were relatively lower(P<0.05),and heart weight indexes as well as the levels of TGF- β1 and MMP- 9 were relatively higher(P<0.05). Conclusion: Huoxu Tongmai prescription can significantly improve the heart function, myocardial fibrosis, and myocardial cell energy metabolism of CHF rats. Its mechanism may be related to the up-regulation of the expressions of AMPK and PGC-1α as well as the down-regulation of the levels of TGF-β1 and MMP-9.

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王巍,罗玉寅,廖骏.活血通脉方对慢性心力衰竭大鼠心肌纤维化和心肌细胞能量代谢的影响研究[J].新中医,2020,52(22):1-5

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  • 在线发布日期: 2020-11-27
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