Effect of <i>β</i>-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism

LIU Wei; HE Jun; HOU Ling; WANG Tao; JI Fang

doi:10.11665/j.issn.1000-5048.20220510

Journal of China Pharmaceutical University > 2022 > 53(5): 599-605. > DOI: 10.11665/j.issn.1000-5048.20220510

LIU Wei, HE Jun, HOU Ling, WANG Tao, JI Fang. Effect of β-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism[J]. Journal of China Pharmaceutical University, 2022, 53(5): 599-605. DOI: 10.11665/j.issn.1000-5048.20220510

Citation:

PDF (753 KB)

Effect of β-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism

1.
Department of Pharmaceutics, Nanjing Prevention and Treatment Center for Occupational Diseases, Nanjing 210042
2.
Center for New Drug Screening, Institute of Pharmaceutical Research, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the Project of Nanjing Health Science and Technology Development (No.YKK21188)

More Information

Received Date: April 02, 2022
Revised Date: June 26, 2022

Graphical Abstract

Abstract

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.
- β-nicotinamide mononucleotide,
- pneumoconiosis,
- respiratory muscle fatigue,
- mitochondrion

FullText(HTML)

References (23)

References

[1]	.J Environ Occup Med（环境与职业医学），2018，35（8）：677-689.
[2]	Yan P，Ye LB，Chen WQ. Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease［J］. J China Pharm Univ（中国药科大学学报），2021，52（2）：144-155.
[3]	Langer D，Charususin N，Jácome C，et al. Efficacy of a novel method for inspiratory muscle training in people with chronic obstructive pulmonary disease［J］. Phys Ther，2015，95（9）：1264-1273.
[4]	Yin PY，Chen FQ. Research progress of TCM treatment of ventilator fatigue in acute phase of chronic obstructive pulmonary disease［J］. Mod J Integr Tradit Chin West Med（现代中西医结合杂志），2021，30（35）：3987-3990.
[5]	Romani M，Sorrentino V，Oh CM，et al. NADPLA⁺ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle［J］. Cell Rep，2021，34（3）：108660.
[6]	She J，Sheng R，Qin ZH. Pharmacology and potential implications of nicotinamide adenine dinucleotide precursors［J］. Aging Dis，2021，12（8）：1879-1897.
[7]	Liu W，Jiang SF，Tu L，et al. Mechanism of JinShuiBao capsule in ameliorating rat pneumoconiosis model［J］. J China Pharm Univ（中国药科大学学报），2018，49（4）：476-482.
[8]	Jiao GY，Li CF，Tan ST，et al. Effect of end-expiratory positive pressure on contractile function and ultrastructure of diaphragm［J］. Med J Chin PLA（解放军医学杂志），2008，33（6）：676-679.
[9]	Wang J，Jiang SF，Hu WY，et al. Pharmacodynamic study on Jinshuibao Capsules on rat pneumoconiosis model［J］. Occup Health（职业与健康），2018，34（13）：1772-1776.
[10]	Uddin GM，Youngson NA，Sinclair DA，et al. Head to head comparison of short-term treatment with the NAD（+） precursor nicotinamide mononucleotide （NMN） and 6 weeks of exercise in obese female mice［J］. Front Pharmacol，2016，7：258.
[11]	Hu T，Zhou XY，Xue D，et al. Protective effect of modified sijunzi decoction against diaphragmatic mitochondria injury of mice with chronic obstructive pulmonary disease［J］. J Guangzhou Univ Tradit Chin Med（广州中医药大学学报），2020，37（3）：523-527.
[12]	Ye B，Li FX. Clinical studies on the functions of mitochondrial function of intercostal muscles in patients with chronic obstruction pulmonary disease［J］. Chin J Lung Dis Electron Ed（中华肺部疾病杂志电子版），2018，11（5）：544-550.
[13]	Puente-Maestu L，Pérez-Parra J，Godoy R，et al. Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients［J］. Eur Respir J，2009，33（5）：1045-1052.
[14]	Davila A，Liu L，Chellappa K，et al. Nicotinamide adenine dinucleotide is transported into mammalian mitochondria［J］. eLife，2018，7：e33246.
[15]	Fletcher RS，Ratajczak J，Doig CL，et al. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells［J］. Mol Metab，2017，6（8）：819-832.
[16]	Xue CL，Zhuge YL，Zeng JX. Improved effect of curcumin on mitochondrial dysfunction induced by high glucose in L6 cells［J］. J China Pharm Univ（中国药科大学学报），2016，47（3）：342-347.
[17]	Taylor DF，Bishop DJ. Transcription factor movement and exercise-induced mitochondrial biogenesis in human skeletal muscle：current knowledge and future perspectives［J］. Int J Mol Sci，2022，23（3）：1517.
[18]	Sligar J，DeBruin DA，Saner NJ，et al. The importance of mitochondrial quality control for maintaining skeletal muscle function across health span［J］. Am J Physiol Cell Physiol，2022，322（3）：C461-C467.
[19]	Huang RX，Tao J. Nicotinamide mononucleotide attenuates glucocorticoid-induced osteogenic inhibition by regulating the SIRT1/PGC-1α signaling pathway［J］. Mol Med Rep，2020，22（1）：145-154.
[20]	Rajabi M，Vafaee MS，Hosseini L，et al. Pretreatment with nicotinamide mononucleotide increases the effect of ischaemic postconditioning on cardioprotection and mitochondrial function following ex vivo myocardial reperfusion injury in aged rats［J］. Clin Exp Pharmacol Physiol，2022，49（4）：474-482.
[21]	Parry HA，Roberts MD，Kavazis AN. Human skeletal muscle mitochondrial adaptations following resistance exercise training［J］. Int J Sports Med，2020，41（6）：349-359.
[22]	Philp AM，Saner NJ，Lazarou M，et al. The influence of aerobic exercise on mitochondrial quality control in skeletal muscle［J］. J Physiol，2021，599（14）：3463-3476.
[23]	Wahwah N，Kras KA，Roust LR，et al. Subpopulation-specific differences in skeletal muscle mitochondria in humans with obesity：insights from studies employing acute nutritional and exercise stimuli［J］. Am J Physiol Endocrinol Metab，2020，318（4）：E538-E553.

[1]	SHUAI Yubing, WANG Qiudan, HE Tianyu, CAO Lijuan. Mitofusin 2: an emerging drug target[J]. Journal of China Pharmaceutical University, 2025, 56(1): 1-9. DOI: 10.11665/j.issn.1000-5048.2024041001
[2]	LIU Wei, JIANG Shufan, TU Lei, HU Weiyi, WANG Tao, WANG Jing. Mechanism of JinShuiBao capsule in ameliorating rat pneumoconiosis model[J]. Journal of China Pharmaceutical University, 2018, 49(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20180414
[3]	XUE Chunling, ZHUGE Yuanli, ZENG Jingxia. Improved effect of curcumin on mitochondrial dysfunction induced by high glucose in L6 cells[J]. Journal of China Pharmaceutical University, 2016, 47(3): 342-347. DOI: 10.11665/j.issn.1000-5048.20160316
[4]	ZHANG Bingfeng, JIANG Hulin. Construction and characterization of mitochondria-targeted TPP-PEI-LND[J]. Journal of China Pharmaceutical University, 2015, 46(6): 659-664. DOI: 10.11665/j.issn.1000-5048.20150604
[5]	FENG Quanfu, BI Lei, YAN Xiaojing, YANG Ye, CHEN Weiping. Inhibition of tetramethypyrazine on proliferation of HepG2 cells and its effects on the pathway of mitochondrial apoptosis[J]. Journal of China Pharmaceutical University, 2015, 46(3): 350-354. DOI: 10.11665/j.issn.1000-5048.20150315
[6]	Study on the Relationship of Dexamethasone-induced Mouse Thymocytes Apoptosis Process with ERK1/2 MAPK Pathway and Calcium Ion Concentration[J]. Journal of China Pharmaceutical University, 2004, (1): 79-83.
[7]	Effects of the Crude Saponins in Sheng-mai-san, Radix Geseng and Radix Ophiopogonis on the Respiratory Burst Induced by Different Stimulants in Rat Polymorphonuclear Leukocyte[J]. Journal of China Pharmaceutical University, 2001, (5): 66-69.
[8]	Reducing L-Thyroxine Cardiac Hypertrophy and Suppressing Mitochon-drial Calcium Pump by Propranolol,Verapamil and Captopril[J]. Journal of China Pharmaceutical University, 1996, (1): 47+44-47.
[10]	Effect of Dauricine Derivative D_3 on Respiration and Its Antagonism of Respiratory Inhibition Induced by Morphine and Xylazine[J]. Journal of China Pharmaceutical University, 1993, (2): 91-94.

Cited By

Get Citation

PDF

XML

Article views (189) PDF downloads (387)

Turn off MathJax

Article Contents

Abstract

References

Effect of β-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism

Abstract

References

Related Articles

Catalog

Effect of β-nicotinamide mononucleotide on respiratory muscle fatigue in pneumoconiosis rats and its mitochondrial mechanism

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content