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生脉饮对阿霉素诱导的 Wistar 大鼠心肌损伤的心脏保护作用。

Cardioprotection of Sheng Mai Yin a classic formula on adriamycin induced myocardial injury in Wistar rats.

机构信息

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.

出版信息

Phytomedicine. 2018 Jan 1;38:1-11. doi: 10.1016/j.phymed.2017.09.001. Epub 2017 Oct 25.

DOI:10.1016/j.phymed.2017.09.001
PMID:29425641
Abstract

BACKGROUND

Sheng Mai Yin (SMY), a well-known Chinese herbal medicine, is widely used to treat cardiac diseases characterized by the deficiency of Qi and Yin syndrome in China. SMY-based treatment has been derived from Traditional Chinese Medicine (TCM), officially recorded in the Chinese Pharmacopoeia.

PURPOSE

We aimed to clarify whether SMY attenuates myocardial injury induced by adriamycin in Wistar rats with chronic heart failure (CHF).

METHODS

To quantify ginsenoside Rg1, ophiopogonin D, ophiopogonin D', schisandrin by HPLC. To establish CHF animal model, adriamycin was intraperitoneally injected in Wistar rats for 7 weeks at a dose of 2 mg/kg body weight. Overall, 180 rats were randomly assigned to six groups: control, CHF model, captopril (positive control), high dose (HSMY), medium dose (MSMY), and low dose (LSMY). Experimental rats were fed 0.625 mg/kg captopril and 90 mg/kg, 45 mg/kg, and 22.5 mg/kg SMY, respectively, over 7 weeks. The inflammatory cytokines TNF-α and IL-6 were measured using ELISA. Matrix metalloproteinases (MMPs) were identified using immunohistochemistry (IHC). Both IHC and RT-PCR were used for quantification of COL-IV expression levels in the heart tissues. Scanning electron microscopy (SEM) was used for the visualization of myocardium morphology.

RESULTS

The concentration of ginsenoside Rg1, ophiopogonin D, ophiopogonin D' and schisandrin in SMY was found to be 25.63 ± 3.42 mg, 11.00 ± 1.17 mg, 7.02 ± 0.51 mg, and 25.31 ± 4.28 mg per gram of SMY, respectively. Compared with CHF model group, TNF-α levels were significantly lower (p < .01) in the four drug-administered groups. Moreover, except in the SYM low dose group, IL-6 levels in the other 3 drug-administered groups were also significantly reduced (p < .01). COL-IV expression was also significantly reduced on treatment with high SYM dose (p < .05). IHC results confirmed that SMY and captopril significantly reduced MMPs expression in the heart.

CONCLUSION

SMY could control or slow CHF progression by suppressing pathological changes in the myocardium in CHF models. This could be attributed at least partly to the downregulation of IL-6 and TNF-α and inhibition of overexpression of MMPs and COL-IV, which significantly relieved the cardiac-linked pathologies, decreased the risk of myocardial fibrosis, and inhibited cardiac remodeling. These findings suggested that SMY and captopril have similar efficacy for the treatment of adriamycin-induced myocardial injury. In addition, Chinese herbal preparation SMY may play a role in the treatment of cardiac diseases.

摘要

背景

生脉饮(SMY)是一种著名的中草药,在中国被广泛用于治疗气阴两虚型心脏病。SMY 的治疗方法来源于中药(TCM),并在《中国药典》中有正式记载。

目的

本研究旨在阐明生脉饮是否能减轻阿霉素诱导的慢性心力衰竭(CHF)大鼠的心肌损伤。

方法

采用高效液相色谱法(HPLC)定量检测人参皂苷 Rg1、麦冬皂苷 D、麦冬皂苷 D'、五味子醇甲的含量。采用阿霉素腹腔注射的方法建立 CHF 动物模型,剂量为 2mg/kg 体重,每周 1 次,共 7 周。将 180 只大鼠随机分为 6 组:对照组、CHF 模型组、卡托普利(阳性对照)组、高剂量 SMY 组、中剂量 SMY 组、低剂量 SMY 组。实验大鼠分别给予 0.625mg/kg 卡托普利和 90mg/kg、45mg/kg、22.5mg/kg SMY,连续 7 周。采用酶联免疫吸附试验(ELISA)检测肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的水平。采用免疫组织化学(IHC)检测基质金属蛋白酶(MMPs)的表达。IHC 和 RT-PCR 用于检测心脏组织中 COL-IV 的表达水平。扫描电子显微镜(SEM)用于观察心肌形态。

结果

SMY 中人参皂苷 Rg1、麦冬皂苷 D、麦冬皂苷 D'和五味子醇甲的浓度分别为 25.63±3.42mg/g、11.00±1.17mg/g、7.02±0.51mg/g和 25.31±4.28mg/g。与 CHF 模型组相比,四组药物治疗组 TNF-α水平均显著降低(p<0.01)。此外,除低剂量 SMY 组外,其他 3 组药物治疗组的 IL-6 水平也显著降低(p<0.01)。高剂量 SMY 组 COL-IV 的表达也显著降低(p<0.05)。IHC 结果证实,SMY 和卡托普利可显著降低 CHF 模型中心脏 MMPs 的表达。

结论

SMY 通过抑制 CHF 模型中心肌的病理变化,可控制或减缓 CHF 的进展。这至少部分归因于 IL-6 和 TNF-α 的下调,以及 MMPs 和 COL-IV 过度表达的抑制,从而显著缓解心脏相关病变,降低心肌纤维化风险,抑制心脏重构。这些发现表明,SMY 和卡托普利对阿霉素诱导的心肌损伤具有相似的治疗效果。此外,中药复方 SMY 可能在心脏疾病的治疗中发挥作用。

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