1 Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, China.
2 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Aerosol Med Pulm Drug Deliv. 2019 Apr;32(2):70-77. doi: 10.1089/jamp.2018.1453. Epub 2019 Jan 25.
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-Smad and tumor growth factor (TGF)-β 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-β mRNA, TGF-β protein, and P-Smad in the NANM group were markedly decreased.
NANM ameliorated OVA-induced airway remodeling, partly through regulation of the TGF-β/Smad pathway.
气道重塑被认为是难治性和不可控性哮喘的一个重要因素。既往研究证实，抗神经生长因子（NGF）抗体可改善气道重塑。然而，雾化吸入抗 NGF 微球（NANM）是否能抑制气道重塑尚不清楚。本研究旨在探讨 NANM 对卵清蛋白（OVA）诱导的气道重塑及其机制的影响。
采用聚合物合金法制备抗 NGF 微球。用 OVA 建立大鼠哮喘气道重塑模型。用雾化吸入抗 NGF 抗体或 NANM 处理大鼠。检测气道炎症、气道反应性和气道重塑。还检测了肺组织 P-Smad 和转化生长因子（TGF）-β mRNA 和蛋白的表达。
抗 NGF 抗体微球包封率高，释放时间长。NANM 明显减轻 OVA 诱导的气道重塑，如胶原沉积、平均气道阻力、WAm/Pbm、WAt/Pbm 和 Wcol/Pbm 比值（WAt，支气管壁面积；Pbm，基底膜周长；WAm，平滑肌壁面积；Wcol，气道胶原纤维面积）。与抗 NGF 抗体组和 OVA 组相比，NANM 组 TGF-β mRNA、TGF-β 蛋白和 P-Smad 的表达明显降低。
NANM 改善 OVA 诱导的气道重塑，部分通过调节 TGF-β/Smad 通路。
