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雄性豚鼠的缺血/再灌注损伤:一种用于研究心血管并发症中心肌损伤的有效模型。

Ischemia/reperfusion injury in male guinea pigs: An efficient model to investigate myocardial damage in cardiovascular complications.

机构信息

Drug Discovery and Molecular Cardiology Laboratory, Department of Bioinformatics, Bharathidasan University, Tiruchirappalli, 620024, India.

Molecular Gerontology Laboratory, Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620024, India.

出版信息

Biomed Pharmacother. 2018 Mar;99:469-479. doi: 10.1016/j.biopha.2018.01.087. Epub 2018 Feb 20.

Abstract

Myocardial ischemia/reperfusion (I/R) injury is the major problem that aggravates cardiac damage. Several established animal models fail to explain the similarity in disease mechanism and progression as seen in humans; whereas guinea pig shows high similarity in cardiovascular parameters. Hence, current study is aimed to develop an animal model using guinea pigs that may best correlate with disease mechanism of human myocardial I/R injury. Male guinea pigs were randomized into three groups: normal diet (ND), high fat diet (HFD) and sham; fed with respective diets for 90 days. Myocardial infarction (MI) was induced by ligating left anterior descending artery (LAD) for 30 min followed by 24 h and 7 days of reperfusion in ND and HFD groups. Electrocardiogram (ECG) showed the alterations in electrical conduction during myocardial I/R injury. Elevated levels of lactate dehydrogenase (LDH) and creatine kinase-MB ((CK-MB)) were higher in HFD compared to ND. Inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were up-regulated in I/R injury animals compared to sham. Fold change of these protein expression levels were higher in HFD compared to ND. Elevated lipid profile and increased aortic wall thickness in HFD animals depicts the risk of developing cardiovascular complications. ECG analysis strongly confirmed MI through changes in sinus rhythm that are reflected in infarcted tissue as verified through TTC staining. Thus the combination of HFD followed by I/R injury proved to be an efficient model to study pathophysiology of myocardial I/R injury with minimal tissue damage and surgical mortality.

摘要

心肌缺血/再灌注(I/R)损伤是加重心脏损伤的主要问题。一些已建立的动物模型未能解释与人类所见疾病机制和进展相似的情况;而豚鼠在心血管参数方面表现出高度相似性。因此,目前的研究旨在建立一种使用豚鼠的动物模型,该模型可能与人类心肌 I/R 损伤的疾病机制最佳相关。雄性豚鼠随机分为三组:正常饮食(ND)、高脂肪饮食(HFD)和假手术;分别用相应的饮食喂养 90 天。通过结扎左前降支(LAD)诱导心肌梗死(MI)30 分钟,然后在 ND 和 HFD 组中再灌注 24 小时和 7 天。心电图(ECG)显示心肌 I/R 损伤期间电传导的变化。HFD 组的乳酸脱氢酶(LDH)和肌酸激酶同工酶-MB(CK-MB)水平升高高于 ND 组。与假手术相比,I/R 损伤动物的炎症标志物如肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平上调。与 ND 相比,这些蛋白表达水平的倍数变化在 HFD 中更高。HFD 动物的脂质谱升高和主动脉壁厚度增加表明发生心血管并发症的风险增加。ECG 分析通过窦性节律的变化强烈证实了 MI,这些变化反映在 TTC 染色证实的梗死组织中。因此,HFD 后再灌注损伤的组合被证明是研究心肌 I/R 损伤病理生理学的有效模型,具有最小的组织损伤和手术死亡率。

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