Nebulized Inhalation of Anti-Nerve Growth Factor Microspheres Inhibits Airway Remodeling in an Ovalbumin-Induced Rat Asthma Model
Nebulized Inhalation of Anti-Nerve Growth Factor Microspheres Inhibits Airway Remodeling in an Ovalbumin-Induced Rat Asthma Model
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DOI：
10.1089/jamp.2018.1453
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Lin, Yun
中科院分区：
文献类型：
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作者：
She, Weiwei;Mei, Zhengmin;Lin, Yun
背景：气道重塑被认为是难治性和无法控制的哮喘的重要因素。已有研究证实抗神经生长因子（NGF）抗体可改善气道重塑。然而，雾化吸入抗神经生长因子微球（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）诱导的气道重塑的影响及其机制。方法：采用高分子合金法制备抗NGF微球。用卵清蛋白建立大鼠哮喘气道重塑模型。雾化吸入抗NGF抗体或NANM治疗大鼠。测量气道炎症、气道反应性和气道重塑。同时检测肺组织P-Smad（3）和肿瘤生长因子（TGF）-β（1）mRNA和蛋白表达。结果：抗NGF抗体微球包封率高，释放时间长。NANM显著减弱OVA诱导的气道重塑，如胶原沉积、平均肺阻力、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 1 mRNA、TGF-β 1蛋白和P-Smad（3）的表达均显著降低。结论：NANM部分通过调节TGF-β（1）/Smad（3）信号通路减轻OVA诱导的气道重塑。
Background: 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. Methods: 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(3) and tumor growth factor (TGF)-beta(1) mRNA and protein expression were also measured. Results: 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-beta(1) mRNA, TGF-beta(1) protein, and P-Smad(3) in the NANM group were markedly decreased. Conclusions: NANM ameliorated OVA-induced airway remodeling, partly through regulation of the TGF-beta(1)/Smad(3) pathway.