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阿替洛尔改善大鼠因石膏固定引起的骨骼肌萎缩和氧化应激。

Atenolol Ameliorates Skeletal Muscle Atrophy and Oxidative Stress Induced by Cast Immobilization in Rats.

作者信息

Kumar Anand, Raorane Chaitany Jayprakash, Rawat Deepak, Prajapati Priyanka, Raj Ritu, Kumar Dinesh, Kim Seong-Cheol, Raj Vinit, Kushwaha Sapana

机构信息

Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.

出版信息

Biomedicines. 2023 Apr 25;11(5):1269. doi: 10.3390/biomedicines11051269.

Abstract

(1) Background: Skeletal muscle atrophy is a common and debilitating condition associated with disease, bed rest, and inactivity. We aimed to investigate the effect of atenolol (ATN) on cast immobilization (IM)-induced skeletal muscle loss. (2) Methods: Eighteen male albino Wistar rats were divided into three groups: a control group, an IM group (14 days), and an IM+ATN group (10 mg/kg, orally for 14 days). After the last dose of atenolol, forced swimming test, rotarod test, and footprint analysis were performed, and skeletal muscle loss was determined. Animals were then sacrificed. Serum and gastrocnemius (GN) muscles were then collected, serum creatinine, GN muscle antioxidant, and oxidative stress levels were determined, and histopathology and H NMR profiling of serum metabolites were performed. (3) Results: Atenolol significantly prevented immobilization-induced changes in creatinine, antioxidant, and oxidative stress levels. Furthermore, GN muscle histology results showed that atenolol significantly increased cross-sectional muscle area and Feret's diameter. Metabolomics profiling showed that glutamine-to-glucose ratio and pyruvate, succinate, valine, citrate, leucine, isoleucine, phenylalanine, acetone, serine, and 3-hydroxybutyrate levels were significantly higher, that alanine and proline levels were significantly lower in the IM group than in the control group, and that atenolol administration suppressed these metabolite changes. (4) Conclusions: Atenolol reduced immobilization-induced skeletal muscle wasting and might protect against the deleterious effects of prolonged bed rest.

摘要

(1) 背景:骨骼肌萎缩是一种与疾病、卧床休息和缺乏运动相关的常见且使人衰弱的病症。我们旨在研究阿替洛尔(ATN)对石膏固定(IM)诱导的骨骼肌损失的影响。(2) 方法:将18只雄性白化Wistar大鼠分为三组:对照组、IM组(14天)和IM + ATN组(10 mg/kg,口服14天)。在最后一剂阿替洛尔给药后,进行强迫游泳试验、转棒试验和足迹分析,并测定骨骼肌损失情况。然后处死动物。接着收集血清和腓肠肌(GN),测定血清肌酐、GN肌肉抗氧化剂和氧化应激水平,并进行血清代谢物的组织病理学和1H NMR分析。(3) 结果:阿替洛尔显著预防了固定诱导的肌酐、抗氧化剂和氧化应激水平的变化。此外,GN肌肉组织学结果显示,阿替洛尔显著增加了肌肉横截面积和费雷特直径。代谢组学分析表明,IM组中谷氨酰胺与葡萄糖的比率以及丙酮酸、琥珀酸、缬氨酸、柠檬酸、亮氨酸、异亮氨酸、苯丙氨酸、丙酮、丝氨酸和3-羟基丁酸的水平显著高于对照组,丙氨酸和脯氨酸水平显著低于对照组,而给予阿替洛尔可抑制这些代谢物变化。(4) 结论:阿替洛尔减少了固定诱导的骨骼肌萎缩,并可能预防长期卧床休息的有害影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c019/10215752/e0cf19b2ea3f/biomedicines-11-01269-g001.jpg

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