Transcriptomic Insights into Different Stimulation Intensity of Electroacupuncture in Treating COPD in Rat Models

Area of Science:

• Integrative and Complementary Medicine
• Pulmonology
• Molecular Biology

Background:

• Electroacupuncture (EA) shows therapeutic potential for chronic obstructive pulmonary disease (COPD).
• Previous studies lack comprehensive investigation into intensity-dependent EA effects (1mA vs. 3mA) and underlying molecular mechanisms in COPD.
• Understanding these differences is crucial for optimizing EA therapy.

Purpose of the Study:

• To investigate the intensity-specific effects of EA (1mA and 3mA) on a rat model of COPD.
• To elucidate the molecular mechanisms, including gene expression patterns and key regulatory pathways, influenced by different EA intensities.
• To identify potential therapeutic targets for COPD treatment using EA.

Main Methods:

• Established a COPD rat model using chronic cigarette smoke exposure and lipopolysaccharide instillation.
• Administered EA at 1mA and 3mA to acupoints BL13 and ST36 for 2 weeks.
• Evaluated therapeutic effects via pulmonary function tests, histopathology, inflammatory cytokine analysis, and oxidative stress markers.
• Utilized transcriptome profiling and Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene expression patterns and hub genes.
• Validated key gene expression at mRNA and protein levels using RT-qPCR and Western blot.

Main Results:

• Both 1mA and 3mA EA improved lung function, reduced inflammation, and alleviated oxidative stress in COPD rats, with differing effects.
• Transcriptome analysis revealed distinct gene expression profiles for each EA intensity, highlighting shared and specific enriched pathways.
• Eight candidate genes (e.g., Aqp9, Trem1, Mrc1, Gpnmb) were identified as differentially expressed, with some intensity-specific changes (e.g., Msr1, Slc26a4 for 1mA; Pde3a, Bmp6 for 3mA).
• WGCNA identified 5 key modules and module-trait relationships, emphasizing the identified candidate genes.

Conclusions:

• EA at 1mA and 3mA intensities induce distinct transcriptional changes in COPD rats.
• These intensity-specific pathways offer insights into the differential mechanisms of EA therapy.
• Genes such as Mrc1, Gpnmb, Trem1, and Aqp9 are promising targets for further investigation in COPD treatment.
• Further research is warranted to fully understand the functional roles of these identified genes in COPD pathogenesis and EA treatment response.