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程彬,胡志希,李琳,钟森杰,邱宏.基于能量代谢探讨参麦注射液对高血压心衰的干预机制[J].湖南中医药大学学报,2021,41(8):1172-1177[点击复制] |
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基于能量代谢探讨参麦注射液对高血压心衰的干预机制 |
程彬,胡志希,李琳,钟森杰,邱宏 |
(湖南中医药大学, 湖南 长沙 410208) |
摘要: |
目的 研究参麦注射液对高血压心衰大鼠能量代谢的影响,揭示药物干预机制。方法 通过高盐饲料喂养Dah1/SS盐敏感大鼠复制高血压心衰模型,成模大鼠随机分为模型组和参麦注射液组[大鼠腹腔注射参麦注射液6.0 mL/(kg·d)],另设普通饲料喂养的正常组。药物干预15 d,运用心脏彩超检测左室射血分数值(left ventricular ejection fraction,LVEF)与左室短轴缩短率值(left ventricular fractional shortening,LVFS),ELISA法检测血清单磷酸腺苷(adenosine monophosphate,AMP)、二磷酸腺苷(adenosine diphosphate,ADP)、三磷酸腺苷(adenosine diphosphate,ADP)、N端前脑钠肽(N-terminal pro-brain natriuretic peptide,NT-proBNP)含量;透射电镜观察心肌细胞线粒体形态结构变化;Western blot法检测大鼠心肌组织中腺苷酸激活蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)、过氧化物酶体增殖物激活受体α(peroxisome proliferator activated receptorsα,PPARα)、PPARγ辅激活因子1α(proliferator-activated receptor gamma costimulator 1-α,PGC-1α)的蛋白表达量。结果 与正常组相比,模型组大鼠心肌细胞线粒体排列紊乱、形态扭曲、结构破坏,心功能障碍;血清ATP显著降低(P<0.01)、ADP上升(P<0.05)、AMP上升显著(P<0.01);心肌组织的AMPK表达上升(P<0.01),PPARα、PGC-1α降低(P<0.01)。与模型组相比,参麦注射液组大鼠心肌线粒体排列相对整齐,结构恢复,心功能改善;ATP含量上升(P<0.01)、AMP含量下降(P<0.05);AMPK降低(P<0.01)、PPARα与PGC-1α上升(P<0.01)。结论 参麦注射液通过调控AMPK、PPARα、PGC-1α相关蛋白表达,恢复线粒体结构和功能,促进ATP生成,改善能量代谢障碍,从而优化心功能。 |
关键词: 慢性心力衰竭 高血压 参麦注射液 线粒体 能量代谢 |
DOI:10.3969/j.issn.1674-070X.2021.08.007 |
投稿时间:2021-04-22 |
基金项目:国家自然科学基金项目(81774208);湖南省自然科学基金项目(2020JJ4062,2020JJ5408,2019JJ50447)。 |
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Intervention Mechanism of Shenmai Injection on Hypertensive Heart Failure Based on Energy Metabolism |
CHENG Bin,HU Zhixi,LI Lin,ZHONG Senjie,QIU Hong |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
Abstract: |
Objective To study the effect of Shenmai Injection on energy metabolism of hypertensive heart failure rats and reveal the mechanism of drug intervention. Methods The hypertensive heart failure model was established by feeding Dah1/SS salt-sensitive rats with high-salt diet. The model rats were randomly divided into model group and Shenmai Injection group[rats were intraperitoneally with Shenmai Injection 6.0 mL/(kg·d)], and the normal group fed with ordinary diet was additionally set up. After 15 days of drug intervention, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by cardiac color Doppler ultrasonography. Serum adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA The morphological and structural changes of mitochondria of myocardial cells were observed by transmission electron microscopy. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator activated receptors α (PPARα) and PPARγ coactivator 1α (PGC-1α) in rat cardiac tissue were detected by Western blot. Results Compared with the normal group, the mitochondria in the model group were disordered, distorted and destroyed, and the cardiac function was impaired; serum ATP was significantly decreased (P<0.01), ADP was increased (P<0.05), and AMP was significantly increased (P<0.01); the expression of AMPK in myocardial tissue was increased (P<0.01), while PPARα and PGC-1α were decreased (P<0.01). Compared with model group, the myocardial mitochondria of rats in Shenmai Injection group were arranged relatively neatly, the structure was restored and the cardiac function was improved; ATP content increased (P<0.01), AMP content decreased (P<0.05); AMPK decreased (P<0.01), PPARα and PGC-1α increased (P<0.01). Conclusion By regulating the expression of AMPK, PPARα and PGC-1α-related proteins, Shenmai Injection can restore the structure and function of mitochondria, promote the generation of ATP and improve the energy metabolism disorder, so as to optimize the cardiac function. |
Key words: chronic heart failure hypertension Shenmai Injection mitochondria energy metabolism |
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