Chronic obstructive pulmonary disease (COPD) is the most common chronic airway disease in the world, and most patients have emphysema in the imaging sense.
Emphysema is usually related to tobacco exposure, and prolonged tobacco exposure can cause lung damage. Lung and systemic inflammation, alveolar epithelial cell apoptosis, accelerated aging, oxidative stress, and also induce cytotoxin accumulation, unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. Lead to apoptosis and inflammation of cells. Coupled with mitochondrial dysfunction and incomplete decomposition of damaged mitochondria , it indicates that accelerated aging may be a potential mechanism leading to the development of emphysema.
However, the current treatment for emphysema is usually based on the use of inhaled drugs, which can help improve respiratory symptoms and lung function, but have limited systemic effects on lung tissue regeneration and disease.
Metformin is a drug for the treatment of type 2 diabetes and is also beneficial to aging-related diseases. Therefore, researchers speculate that metformin can improve emphysema caused by tobacco exposure. And against this background, animal experiments and retrospective population studies were carried out.
Research method
➤Animal experiment: The mice were exposed to tobacco for up to 24 weeks, and some mice were fed with metformin after 12 weeks. After the experiment, the mouse lung, kidney, and muscle lesions were detected, and the potential mechanism of metformin was explored.
➤Retrospective population study: The study collected data from the COPDGene study and assessed whether the subjects used it during follow-up The relationship between metformin and emphysema progression index and adjusted lung density (ALD).
research results
➤Research findings,Metformin is effective in tobacco-induced lung inflammation, air cavity enlargement, small airway remodeling, glomerular contraction, oxidative stress, apoptosis, telomere damage, aging, metabolic disorders in vivo and in vitro, and endoplasmic reticulum response Excitation has a protective effect.
➤AMPK pathway is the core pathway of metformin protection.
➤In COPD Gene, subjects who took metformin had a slower progression of emphysema compared with subjects who did not take metformin (-0.92%; 95%CI -1.7%~-0.14%; p=0.02), ALD decreased more slowly (2.2g/L; 95%CI 0.43~4.0g/L, p=0.01)
research results
metformin on lung and kidney of mice induced by smoke exposure It has a protective effect on muscle damage, mitochondrial dysfunction, and UPR-ER stress.
In humans, the use of metformin may also delay the progression of emphysema.
Although this study is an animal experiment and a retrospective study, it provides new insights in the treatment of emphysema, which has the effect of inspiring others. At present, most of the drug treatments for emphysema are symptomatic treatment, and how to delay the progression of the disease is still the focus of future research.
References:
Polverino F, Wu TD, Rojas-Quintero J, et al. Am J Respir Crit Care Med. 2021 May 25.
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