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脂联素在伴有心功能障碍的 2 型糖尿病大鼠发病和进展中的作用。

Adiponectin in onset and progression of T2DM with cardiac dysfunction in rats.

机构信息

School of Sciences, Indira Gandhi National Open University (IGNOU), Maidan Garhi, New Delhi, India.

Department of Physiology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.

出版信息

Hum Exp Toxicol. 2020 Nov;39(11):1463-1474. doi: 10.1177/0960327120927446. Epub 2020 Jun 4.

Abstract

Cardiovascular disease and type 2 diabetes mellitus (T2DM) patients have low level of adiponectin, however, till now the role of adiponectin in progression of 'T2DM with cardiac dysfunction' in animal model has not been characterized. Therefore, the aim of the present study was to develop and characterize T2DM animal model with cardiac dysfunction and to study the role of cardiac adiponectin expression in cardiac dysfunction. For this, Wistar rats (M/F) were fed a high-fat diet for different time periods: 3, 4 and 5 weeks and given a single, low-dose streptozotocin (25mg/kg), intraperitoneal injection 1 week prior to the experiments. Rats in T2DM group (3 weeks) developed hyperglycaemia, hyperlipidaemia, oxidative stress with normoinsulinaemia and mild cardiac dysfunction suggesting onset of T2DM with cardiac dysfunction. Extended high-fat feeding, that is, 4 and 5 weeks induced insulin resistance accompanied with cardiac hypertrophy, cardiac dysfunction and reduced baroreflex sensitivity indicating development of T2DM with cardiac dysfunction. Cardiac adiponectin expression did not change in rats of T2DM group (3 weeks), however, it significantly decreased in rats of two T2DM groups (4 and 5 weeks) along with increased intracellular adhesion molecule-1 levels. Thus, the present study for the first time indicates that in the present T2DM animal model, as T2DM progresses cardiac adiponectin expression also decreases which might be the precipitating factor for cardiac hypertrophy and decrease in baroreflex sensitivity, which induces cardiac dysfunction.

摘要

心血管疾病和 2 型糖尿病(T2DM)患者的脂联素水平较低,然而,到目前为止,脂联素在动物模型中“T2DM 伴心功能障碍”进展中的作用尚未确定。因此,本研究的目的是开发和表征具有心功能障碍的 T2DM 动物模型,并研究心脏脂联素表达在心脏功能障碍中的作用。为此,将 Wistar 大鼠(雌雄)用高脂肪饮食喂养不同时间:3、4 和 5 周,并在实验前 1 周给予单次、低剂量链脲佐菌素(25mg/kg)腹腔注射。T2DM 组(3 周)大鼠出现高血糖、高血脂、氧化应激伴正常胰岛素血症和轻度心功能障碍,提示 T2DM 伴心功能障碍的发生。延长高脂肪饮食,即 4 和 5 周,导致胰岛素抵抗,伴有心肌肥厚、心功能障碍和压力感受性反射敏感性降低,表明 T2DM 伴心功能障碍的发展。T2DM 组(3 周)大鼠的心脏脂联素表达没有变化,然而,在两个 T2DM 组(4 和 5 周)大鼠的心脏脂联素表达显著降低,同时细胞间黏附分子-1 水平升高。因此,本研究首次表明,在本 T2DM 动物模型中,随着 T2DM 的进展,心脏脂联素表达也降低,这可能是心肌肥厚和压力感受性反射敏感性降低导致心功能障碍的促成因素。

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