Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus.
Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus.
复制标题
非那利酮减轻2型糖尿病心肌细胞凋亡、代谢紊乱和心肌纤维化。
DOI：
10.1186/s13098-023-01064-3
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发表时间：
2023-04-29
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
芬纳烯酮是第三代矿皮质激素受体拮抗剂，在大规模临床试验中对2型糖尿病患者心功能有良好改善。然而，其在糖尿病性心肌病中的具体作用尚不清楚。我们探讨了芬烯酮在糖尿病性心肌病中的潜在作用和机制。采用高脂饮食加低剂量链脲佐菌素建立2型糖尿病大鼠模型，每组6只。药物组给予细芬烯酮（1 mg/kg/d）治疗，疗程8周。然后检测心脏结构、功能及相关指标。体外培养新生大鼠心肌细胞，观察芬烯酮对高糖、高脂肪酸刺激下心肌细胞的直接影响。与对照组相比，2型糖尿病组大鼠出现高血糖、高脂血症，心功能受损。心肌纤维化和细胞凋亡增加。芬烯酮在不改变血糖水平的情况下减轻了这些损伤。在新生大鼠心肌细胞中，高浓度棕榈酸刺激增加脂肪酸摄取，增加活性氧和细胞凋亡。芬烯酮显著改善脂肪酸代谢，降低细胞炎症水平，减少细胞凋亡。通过阻断矿皮质激素受体，芬烯酮可减轻II型糖尿病大鼠的心脏脂肪变性、心肌纤维化和细胞凋亡，以及随后的心肌重构和舒张功能障碍。在线版本包含补充材料，可在10.1186/s13098-023-01064-3获得。
Finerenone is a third-generation mineralocorticoid receptor antagonists, which has shown good cardiac function improvement in patients with type 2 diabetes in large-scale clinical trials. However, its specific role in diabetic cardiomyopathy remains unclear. We explored the potential functions and mechanisms of finerenone in diabetic cardiomyopathy. The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (n = 6, each group). Next the drug group was treated with finerenone (1 mg/kg/day) for 8 weeks. Then we detected the cardiac structure and function and relevant indicators. Neonatal rat cardiomyocytes were used for in vitro culture to determine the direct effect of finerenone on cardiomyocytes stimulated by high glucose and high fatty acid. Compared with the control group, rats in the type 2 diabetes group exhibited hyperglycemia, hyperlipidemia, and impaired cardiac function. Myocardium showed increased fibrosis and apoptosis. Finerenone attenuated these impairments without changing blood glucose levels. In neonatal rat cardiomyocytes, the stimulation of high concentrations of palmitic acid increased fatty acid uptake, as well as increased reactive oxygen species and apoptosis. Finerenone significantly improved fatty acid metabolism, reduced cellular inflammation levels, and decreased apoptosis. By blocking the mineralocorticoid receptor, finerenone attenuates cardiac steatosis, myocardial fibrosis and apoptosis, and subsequent myocardial remodeling and diastolic dysfunction in type II diabetic rats. The online version contains supplementary material available at 10.1186/s13098-023-01064-3.
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影响因子：
19.6
作者：
Hollenberg, NK;Stevanovic, R;Fisher, NDL
通讯作者：
Fisher, NDL
影响因子：
15.9
作者：
Son, Ni-Huiping;Park, Tae-Sik;Goldberg, Ira J.
通讯作者：
Goldberg, Ira J.
影响因子：
29
作者：
Cheng, Xiang;Geng, Feng;Guo, Deliang
通讯作者：
Guo, Deliang
DOI：
10.1152/ajpheart.00726.2001
发表时间：
2002-02-01
影响因子：
4.8
作者：
Hickson-Bick, DLM;Sparagna, GC;McMillin, JB
通讯作者：
McMillin, JB
DOI：
10.1007/978-1-61779-860-3_5
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Kyrylkova, Kateryna;Kyryachenko, Sergiy;Kioussi, Chrissa
通讯作者：
Kioussi, Chrissa