Comparative analysis of TRPM8 gene and copd markers expression in rat lungs following exposure to cigarette smoke and tobacco aerosol

Background. Chronic Obstructive Pulmonary Disease (COPD) remains a global medical and social problem. The ion channel TRPM8, a cold receptor, is known to be involved in the pathogenesis of the disease. However, existing experimental COPD models often exclude verification of changes in its expression.

Objective. To model COPD-like changes in rats exposed to cigarette smoke and tobacco aerosol, with a comprehensive assessment of morphological changes in lung tissue and the expression level of the TRPM8 gene, as well as key COPD marker genes.

Materials and methods. Male Wistar rats were divided into one control and two experimental groups (n = 30). For 42 days, the first experimental group was subjected to daily inhalation exposure to cigarette smoke (CS), and the second group to tobacco aerosol (TA). On day 42, histological analysis of the lungs and assessment of the expression of COPD marker genes (CCR3, CCL13, COL4A2, IL2RA, VWF) and TRPM8 were performed using RT-PCR.

Results. CS exposure caused significant morphological changes: sclerosis (73.3 % of animals), infiltrate (100 %), emphysema (56.7 %), and goblet cell hyperplasia (90 %) compared to control (p < 0.001). TA led to less pronounced changes, and emphysema was absent. In the CS group, a significant increase in expression was observed: COL4A2 by 63.5-fold, IL2RA by 7.9-fold, CCL13 by 4.7-fold, and TRPM8 by 2.2-fold. In the TA group, expression also increased significantly: COL4A2 by 9.6-fold, IL2RA by 3.0-fold, CCL13 by 7.0-fold, and TRPM8 by 2.6-fold. CS induced a stronger expression of COL4A2 and IL2RA compared to TA.

Conclusion. The model with 42-day CS exposure most adequately reproduces the COPD-like phenotype. Importantly, both experimental models caused a significant increase in the transcription of the cold receptor gene TRPM8, confirming its role in the pathogenesis and revealing new targets for therapy.

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