Nebulized Inhalation of Anti-Nerve Growth Factor Microspheres Inhibits Airway Remodeling in an Ovalbumin-Induced Rat Asthma Model.

Abstract

Airway remodeling is considered an important factor in refractory and uncontrollable asthma. Previous studies have confirmed that anti-nerve growth factor (NGF) antibody can ameliorate airway remodeling. However, whether nebulized inhalation of anti-NGF microspheres (NANM) can inhibit airway remodeling is not clear. The purpose of this study was to investigate the effects of NANM on ovalbumin (OVA)-induced airway remodeling, and the mechanisms involved. Anti-NGF microspheres were produced using a polymer alloy method. OVA was used to establish a rat model of asthma airway remodeling. Rats were treated with inhalation atomized anti-NGF antibody or NANM. Airway inflammation, airway reactivity, and airway remodeling were measured. Lung tissue P-Smad3 and tumor growth factor (TGF)-β1 mRNA and protein expression were also measured. The anti-NGF antibody microsphere encapsulation rate was high, and the release time was long. NANM markedly attenuated OVA-induced airway remodeling, such as collagen deposition, average pulmonary resistance, the WAm/Pbm, WAt/Pbm, and Wcol/Pbm ratios (WAt, bronchial wall area; Pbm, perimeter of basement membrane; WAm, smooth muscle wall area; Wcol, airway collagen fiber area). Compared with the anti-NGF antibody group and the OVA group, the expression of TGF-β1 mRNA, TGF-β1 protein, and P-Smad3 in the NANM group were markedly decreased. NANM ameliorated OVA-induced airway remodeling, partly through regulation of the TGF-β1/Smad3 pathway.