沙丁胺醇改善了链脲佐菌素(STZ)诱导的糖尿病大鼠骨骼肌萎缩和炎症标志物。
Salbutamol ameliorates skeletal muscle wasting and inflammatory markers in streptozotocin (STZ)-induced diabetic rats.
发表日期:2023 Sep 02
作者:
Anand Kumar, Priyanka Prajapati, Vinit Raj, Seong-Cheol Kim, Vikas Mishra, Chaitany Jayprakash Raorane, Ritu Raj, Dinesh Kumar, Sapana Kushwaha
来源:
DIABETES & METABOLISM
摘要:
糖尿病加速肌肉萎缩,导致骨骼肌的恶化。本研究旨在评估β2-肾上腺素能受体激动剂沙丁胺醇(SLB)在链脲佐菌素(STZ)诱导的糖尿病大鼠的肌肉萎缩中的潜在作用。雄性斯普拉格·道利大鼠随机分为四组(n=6):对照组,SLB组,STZ组(单次腹腔注射55 mg/kg),STZ + SLB组(口服沙丁胺醇6 mg/kg,连续4周)。在最后一次SLB剂量后,动物进行了评估肌力和协调能力的测试,包括前肢握力、悬挂丝、活动仪、旋转杆和足迹评估。大鼠随后被牺牲,收集血清和腓肠肌(GN)进行进一步分析。血清评估包括促炎症标志物(肿瘤坏死因子α、白细胞介素-1β、白细胞介素-6)、肌肉标志物(肌酸激酶、肌生成素)、睾酮和脂质标志物。肌肉氧化应激(丙二醛、蛋白质羰基)、抗氧化剂(谷胱甘肽、过氧化氢酶、超氧化物歧化酶)和组织学也进行了检测。此外,进行了1H核磁共振血清代谢组学分析。SLB明显增强了STZ诱导的糖尿病大鼠的肌肉握力、协调能力和抗氧化水平,同时减少了促炎症标志物和氧化应激。降低的血清肌肉生物标志物,增加的睾酮,恢复的脂质水平和改善的肌肉细胞结构表明SLB对糖尿病大鼠的肌肉状况具有积极效果。代谢组学分析显示,STZ组显著增加了苯丙氨酸/酪氨酸比值(PTR)、乳酸/丙酮酸比值(LPR)、乙酸、琥珀酸、异丁酸和组氨酸。SLB治疗恢复了STZ诱导的糖尿病组扰乱的血清代谢物。总之,沙丁胺醇显著保护了STZ诱导的糖尿病大鼠的骨骼肌消耗。版权所有 © 2023 Elsevier B.V. 保留所有权利。
Diabetes accelerates muscle atrophy, leading to the deterioration of skeletal muscles. This study aimed to assess the potential of the β2-adrenoceptor agonist, salbutamol (SLB), to alleviate muscle atrophy in streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were randomized into four groups (n=6): control, SLB, STZ (55 mg/kg, single i.p.), and STZ + SLB (6 mg/kg, orally for 4 weeks). After the final SLB dose, animals underwent tests to evaluate muscle strength and coordination, including forelimb grip strength, wire-hanging, actophotometer, rotarod, and footprint assessments. Rats were then sacrificed, and serum and gastrocnemius (GN) muscles were collected for further analysis. Serum evaluations included proinflammatory markers (tumor necrosis factor α, interleukin-1β, interleukin-6), muscle markers (creatine kinase, myostatin), testosterone, and lipidemic markers. Muscle oxidative stress (malonaldehyde, protein carbonyl), antioxidants (glutathione, catalase, superoxide dismutase), and histology were also performed. Additionally, 1H nuclear magnetic resonance serum profiling was conducted. SLB notably enhanced muscle grip strength, coordination, and antioxidant levels, while reduced proinflammatory markers and oxidative stress in STZ-induced diabetic rats. Reduced serum muscle biomarkers, increased testosterone, restored lipidemic levels, and improved muscle cellular architecture indicated SLB's positive effect on muscle condition in diabetic rats. Metabolomics profiling revealed that the STZ group significantly increased the phenylalanine-to-tyrosine ratio (PTR), lactate-to-pyruvate ratio (LPR), acetate, succinate, isobutyrate, and histidine. SLB administration restored these perturbed serum metabolites in the STZ-induced diabetic group. In conclusion, salbutamol significantly protected against skeletal muscle wasting in STZ-induced diabetic rats.Copyright © 2023 Elsevier B.V. All rights reserved.