[The role of NGF and its receptor TrkA in bronchial asthma and research on targeted therapy for severe asthma using nebulized anti-NGF microspheres].

Objective To investigate the role of nerve growth factor (NGF) and its high-affinity receptor tyrosine kinase A (TrkA) in the pathogenesis of bronchial asthma (BA), and to evaluate their association with asthma severity and type 2 T helper (Th2) inflammatory factors, and to validate the intervention efficacy and mechanism of nebulized targeted therapy using poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with anti-NGF antibodies in severe asthma. Methods Serum samples were collected from asthma patients of varying severity and non-asthmatic individuals. Levels of NGF, TrkA, interleukin 4(IL-4), IL-5, and IL-13 were measured. An ovalbumin (OVA)-induced severe asthma mouse model was established and randomly divided into blank control, severe asthma, conventional antibody therapy, and nebulized anti-NGF microsphere groups. Differences in inflammatory factors in bronchoalveolar lavage fluid (BALF), lung tissue pathology, and NGF/TrkA/NF-κB protein expression levels were compared among groups via ELISA, pulmonary function testing, HE/Masson staining, and Western blot analysis. Results Clinical testing revealed elevated serum NGF (82.52±4.01 vs 22.92±5.25)pg/mL and TrkA (53.93±8.97 vs 15.76±3.60)pg/mL levels in the severe asthma group compared to the non-asthmatic control group; IL-4 (44.23±9.88 vs 20.88±3.90)pg/mL, IL-5 (147.1±14.92 vs 47.13±5.63)pg/mL, and IL-13 (106.9±11.64 vs 51.93±8.55)pg/mL levels were significantly elevated. In animal experiments, the nebulized anti-NGF microsphere group exhibited significantly lower levels of IL-4 (36.08±6.08 vs 87.35±9.13)pg/mL, IL-5 (35.41±4.52 vs 81.53±4.94)pg/mL, and IL-13 (36.37±4.57 vs 92.37±6.53)pg/mL. Forced expiratory volume in one second(FEV1) (84.68±5.33 vs 60.87±3.93)% increased, and airway hyper reactivity(AHR) (152.8±7.36 vs 233.8±8.77)% decreased. Pulmonary tissue pathological damage and collagen deposition were alleviated. Western blot analysis revealed that relative protein levels of NGF, TrkA, and NF-κB in lung tissues of mice treated with nebulized anti-NGF microspheres were lower than those in the severe asthma group. Conclusion The NGF/TrkA signaling pathway is closely associated with asthma severity. Nebulized anti-NGF microsphere therapy effectively targets the lungs, inhibits the NF-κB pathway, alleviates airway inflammation, and significantly improves pulmonary function.