Effect of β-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism
10.11665/j.issn.1000-5048.20220510
- VernacularTitle:β-烟酰胺单核苷酸对尘肺大鼠呼吸肌疲劳的改善作用及其线粒体相关机制
- Author:
Wei LIU
1
;
Jun HE
;
Ling HOU
;
Tao WANG
;
Fang JI
Author Information
1. 南京市职业病防治院药剂科
- Publication Type:Journal Article
- Keywords:
β-nicotinamide mononucleotide;
pneumoconiosis;
respiratory muscle fatigue;
mitochondrion
- From:
Journal of China Pharmaceutical University
2022;53(5):599-605
- CountryChina
- Language:Chinese
-
Abstract:
To explore the effect of β-nicotinamide mononucleotide (NMN) on respiratory muscle function and its mitochondrial related mechanism, the rat model of chronic pneumoconiosis was established by intratracheal injection of quartz dust.Three months after the model was established, the treatment group was given NMN 300 and 150 mg/kg by gavage.All indexes were detected 4 weeks after administration.The results showed that the pneumoconiosis model rats had obvious respiratory abnormalities and ventilation disorders, including the respiratory rate increase, the respiratory amplitude decrease (P < 0.01), the significantly decreased blood pH value, PaO2 and SaO2, and significantly increased PaCO2 (P < 0.01).NMN could significantly improve the respiratory function and increase the blood oxygen saturation of the model rats.It could significantly enhance the contractile function and ATP content of diaphragm and improve muscle fatigue (P < 0.05, P < 0.01).In model rats,the mitochondrial membrane potential of diaphragm and activity of SDH decreased significantly (P < 0.01), while the activity of SOD decreased and the level of MDA increased (P < 0.05), however, NMN could significantly improve oxidative stress and mitochondrial function of diaphragm.NMN could significantly up-regulate the mRNA levels of mitochondrial biogenesis related genes such as Sirt1, Pgc-1α, Nrf1 and Tfam in the diaphragm. In conclusion, this experiment showed that NMN intragastric administration can regulate the function of diaphragm mitochondria in pneumoconiosis model rats, improve diaphragm energy metabolism, enhance diaphragm contraction function, and then improve the state of respiration and ventilation, which may be mediated by promoting the biogenesis of diaphragm mitochondria.
