PDF
Full
Outline
Objective To explore the role and mechanism of β-hydroxy-β-methyl butyric acid (HMB) in intensive care unit-acquired weakness (ICU-AW) associated with acute respiratory distress syndrome (ARDS). Methods Forty SPF grade male C57BL/6 mice were randomly divided into control group, sham operation group, model group, and HMB group, with 10 mice in each group. Model group and HMB group were treated with 3 μg/g lipopolysaccharide (LPS) by intratracheal injection to prepare the ICU-AW model associated with ARDS. Sham operation group received the same amount of sterile water. No procedures for control group. On the second day of modeling, mice in HMB group were given 340 mg/(kg·d) HMB by intragastric administration,and mice in the other three groups were given an equal volume of normal saline for continuous intragastric administration for two weeks. Additional 20 mice were randomized into the ARQ-092 group and Akt inhibitor control group, with 10 mice in each group.On the second day of modeling, both groups were given Akt inhibitor (ARQ-092 group) or an equivalent volume of the carrier (Akt inhibitor control group) orally for 10 hours after HMB intragastric administration for 12 days. We evaluated the grasping force of forelimb muscles and measured the sarcopenia index (SI). HE staining was used to observe the pathological changes in lung and muscle tissues. The mRNA expressions of Akt, FoxO3a, Atrogin1, and MuRF1 in mouse gastrocnemius were tested by qRT-PCR, and the expression levels of Akt/FoxO3a pathway related proteins in mouse gastrocnemius was further detected by Western blotting. Results Compared with the model group, the grasping force and SI of forelimb muscle in HMB group were significantly higher(P<0.05). HE staining revealed regular lung tissue structure in control group and sham operation group. Alveolar septa in model group were thickened and fractured, with structural disorder and inflammatory cell infiltration. The injury degree of lung tissue in HMB group was lighter compared with the model group. We observed normal phenotypes of the muscle tracts of gastrocnemius in control group and sham operation group. In model group, we detected muscle fiber atrophy and decreased quantity, muscle bundle structure destruction, and decreased cross-sectional area. The injury degree of the gastrocnemius muscle in HMB group was mild. In addition, compared with model group, the mRNA expressions of Akt and FoxO3a in the gastrocnemius of HMB group were significantly increased (P<0.05), and the phosphorylation levels of Akt and FoxO3a protein were also increased (P<0.05), the levels of Atrogin1 and MuRF1 mRNA and protein expressions decreased (P<0.05). Conclusion HMB can play a protective role in ICU-AW by regulating the Akt-FoxO3A-MurF1/Atrogin1 signaling pathway, which may be valuable for ICU-AW prevention and treatment. The Akt inhibitor ARQ-092 reversed the protective effect of HMB.
PDF
158
63
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
