文章摘要
李晓玲,汪砚雨,徐梅,等.苓桂术甘汤对慢性心律失常大鼠心肌损伤的保护作用及对Nrf2/HO-1通路的影响[J].浙江中医药大学学报,2021,45(8):849-856.
苓桂术甘汤对慢性心律失常大鼠心肌损伤的保护作用及对Nrf2/HO-1通路的影响
Protective Effect of Linggui Zhugan Decoction on Myocardial Injury in Rats with Chronic Arrhythmia and Its Influence on Nrf2/HO-1 Pathway
DOI:10.16466/j.issn1005-5509.2021.08.007
中文关键词: 苓桂术甘汤  慢性心律失常  心肌损伤  核因子E2相关性因子2  血红素氧合酶-1  心肌细胞凋亡  基因表达  蛋白表达
英文关键词: Linggui Zhugan Decoction  chronic arrhythmia  myocardial injury  nuclear factor E2 related factor 2  heme oxygenase-1  apoptosis of cardiomyocytes  gene expression  protein expression
基金项目:河南省医学科技攻关计划项目(2018020855)
作者单位E-mail
李晓玲 河南科技大学第一附属医院 河南洛阳 471003  
汪砚雨 河南科技大学第一附属医院 河南洛阳 471003 wang7896hong@163.com 
徐梅 三门峡市中心医院  
赵子明 郑州市第七人民医院  
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中文摘要:
      [目的]探讨苓桂术甘汤对慢性心律失常大鼠心肌损伤的保护作用及对核因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)/血红素氧合酶-1(heme oxygenase-1,HO-1)通路的影响。[方法]45只雄性SD大鼠中随机选择10只作为正常对照组,其余35只经尾静脉注射氯化钡溶液制备慢性心律失常模型,将30只建模成功的大鼠随机分为苓桂术甘汤组、阳性对照组、模型对照组,每组各10只。苓桂术甘汤组大鼠采用苓桂术甘汤灌胃,阳性对照组采用酒石酸美托洛尔灌胃,模型对照组和正常对照组接受等体积0.9%氯化钠注射液灌胃,2次/d,均干预4周。采用心电图检验大鼠造模成功情况,以酶联免疫吸附法检验大鼠血清谷胱甘肽(glutathione,GSH)、谷胱甘肽硫基转移酶(glutathione S-transferase,GST)含量,苏木精-伊红(hematoxylin-eosin,HE)染色观察心肌组织病理变化,DNA缺口末端标记法(TdT-mediated dUTP nick-end labeling,TUNEL)染色检测各组大鼠心肌细胞凋亡情况,实时荧光定量聚合酶链式反应(Real-time fluorescence quantitative polymerase chain reaction,Real-time qPCR)与Western blot检测心肌组织中Nrf2、HO-1基因及蛋白表达水平。[结果]与正常对照组比较,模型对照组、阳性对照组、苓桂术甘汤组GSH和GST含量较低,心肌细胞凋亡率较高,Nrf2、HO-1 mRNA与蛋白相对表达量较高(P<0.05)。与模型对照组比较,阳性对照组、苓桂术甘汤组大鼠的GSH和GST含量较高,心肌细胞凋亡率较低(P<0.05);与阳性对照组比较,苓桂术甘汤组大鼠的GSH和GST含量较低,心肌细胞凋亡率较高(P<0.05)。模型对照组心肌组织水肿、充血严重,肌束紊乱,心肌细胞间隙增宽;阳性对照组、苓桂术甘汤组心肌组织水肿、肌束及心肌细胞间隙明显改善。与模型对照组比较,阳性对照组、苓桂术甘汤组大鼠Nrf2、HO-1 mRNA及蛋白相对表达量均较高(P<0.05);与阳性对照组比较,苓桂术甘汤组大鼠Nrf2、HO-1 mRNA及蛋白相对表达量均较低(P<0.05)。[结论]苓桂术甘汤可能通过激活Nrf2/HO-1通路,发挥对慢性心律失常大鼠心肌损伤的保护作用。
英文摘要:
      [Objective]To investigate the protective effect of Linggui Zhugan Decoction on myocardial injury in rats with chronic arrhythmia and its effect on nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. [Methods]Ten male SD rats were randomly selected as normal control group from 45 rats, the other 35 rats were injected with barium chloride solution via caudal vein to establish chronic arrhythmia model, 30 successful modeling rats were randomly divided into Linggui Zhugan Decoction group, positive control group and model control group with 10 rats in each group. The rats in Linggui Zhugan Decoction group were given Linggui Zhugan Decoction by gavage, positive control group was given metoprolol tartrate by gavage, model control group and normal control group were given the same volume of 0.9% sodium chloride injection by gavage, twice a day, all rats were intervened for 4 weeks. Electrocardiogram was used to test the success of chronic arrhythmia model. The serum glutathione(GSH) and glutathione S-transferase(GST) were detected by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the pathological changes of myocardium. TdT-mediated dUTP nick-end labeling(TUNEL) staining was used to detect the apoptosis of cardiomyocytes in each group. Real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR) and Western blot were used to detect the mRNA and protein expressions of Nrf2 and HO-1 in myocardial tissue.[Results]Compared with normal control group, the contents of GSH and GST in model control group, positive control group and Linggui Zhugan Decoction group were lower, the apoptosis rate of cardiomyocytes was higher, and the relative expressions of Nrf2 and HO-1 mRNA and protein were higher(P<0.05). Compared with model control group, the contents of GSH and GST in positive control group and Linggui Zhugan Decoction group were higher, and the apoptosis rate of cardiomyocytes was lower(P<0.05); compared with positive control group, the contents of GSH and GST in Linggui Zhugan Decoction group were lower, and the apoptosis rate of cardiomyocytes was higher(P<0.05). In model control group, myocardial tissue edema and hyperemia were serious, myo bundle disorder and myocardial cell gap widened; in positive control group and Linggui Zhugan Decoction group, myocardial tissue edema, muscle bundle and myocardial cell gap were significantly improved. Compared with model control group, the relative expressions of Nrf2 and HO-1 mRNA and protein were higher in positive control group and Linggui Zhugan Decoction group(P<0.05); compared with positive control group, the relative expressions of Nrf2 and HO-1 mRNA and protein in Linggui Zhugan Decoction group were lower(P<0.05). [Conclusion] Linggui Zhugan Decoction may play a protective role on myocardial injury in rats with chronic arrhythmia by activating Nrf2/HO-1 pathway.
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