THE CRITICAL FUNCTION OF MAL GENES IN ASTHMA AND THE POTENTIAL THERAPEUTIC EFFECTS OF CHAI-PU TANG

Abstract

Objective: Myelin and lymphocyte protein (MAL) is a membrane protein with a relative molecular mass of 16.7 kDa that constitutes the microstructural domain of lipid rafts and is associated with the transport of apical proteins in polarized epithelial cells. Gene microarray technology revealed a significant decrease in MAL expression in the lung tissues of asthmatic mice at 2, 4, and 8 weeks, suggesting that changes in MAL expression may be the molecular basis for the development of asthma. Asthma is a common chronic respiratory disease, the main symptoms of which are shortness 7of breath, coughing, chest tightness and wheezing, and can lead to hospitalization or even death in 8 severe cases. However, there is no evidence to support whether the MAL gene is associated with inflammatory changes in the airways during asthma. Methods: Wild-type C57BL/6 mice and wild-type MAL knockout mice at 6-8 weeks of age were obtained and constructed to establish a mouse model of asthma and Hepatic stagnation asthma The model mice were then administered Chai-Pu Tang by gavage. Morphological and structural changes in lung tissues were observed by HE and PAS staining of pathological sections. Eosinophils in the bronchoalveolar lavage fluid (BALF) of mice were counted manually, and the concentrations of interleukin-8 (IL-8), thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33) in the serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein immunoblotting and real-time fluorescence quantitative PCR were used to determine the mRNA and protein expression of MAL, cell adhesion molecule 1 (CADM1), TSLP, IL-8, and IL-33 in lung tissues. Results: After establishing the liver qi stagnation model, we found that MAL knockout mice (MAL^-/-) had a significant increase in body weight from week 2 to week 4 after model establishment. In addition, forced swimming experiments showed that the immobility time of MAL^-/-- mice was significantly increased after model establishment. Tissue staining results showed that the airway structure of each group of mice changed significantly, especially in the MAL^-/--CPD treatment group. Inflammatory factor level detection found that MAL gene knockout aggravated asthma-related airway inflammation and stimulated the production and release of inflammatory factors. Additionally, Chai Pu Tang does not exert anti-inflammatory therapeutic effects after MAL knockout. Conclusion: MAL gene deletion exacerbates inflammatory cell infiltration and promotes the expression of IL-8, IL-33, and TSLP in the lung tissue of mice. The MAL gene shows promise as a potential target for asthma therapy.