Department of Pediatrics, The People's Hospital of Shouguang, Shouguang, 262700, Shandong, China.
Department of Pediatrics, Zaozhuang Municipal Hospital, Zaozhuang, 277100, Shandong, China.
Respir Physiol Neurobiol. 2021 Jun;288:103642. doi: 10.1016/j.resp.2021.103642. Epub 2021 Feb 17.
To investigate the effects of serine protease inhibitor 3n (SerpinA3n) in a neonatal mouse model of asthma.
The study utilized a neonatal mouse ovalbumin (OVA) sensitization model of asthma. Wild type (WT) and SerpinA3n mice were randomly divided into WT/SerpinA3n + saline, WT/SerpinA3n + OVA, WT/SerpinA3n + OVA + rSerpinA3n (recombinant mouse SerpinA3n protein), and WT/SerpinA3n + OVA + DEX (dexamethasone, positive control) groups followed by hematoxylin-eosin (HE) staining, Masson's trichrome stainings, Sircol soluble collagen assay, quantitative real time polymerase chain reaction (qRT-PCR), Western Blot and enzyme linked immunosorbent assay (ELISA).
OVA-induced neonatal mice showed the increases in airway hyper-reactivity with the up-regulated total cells, eosinophil, lymphocyte and neutrophil in bronchoalveolar lavage fluid (BALF), which was much higher in WT + OVA + rSerpinA3n group (P < 0.05). SerpinA3n suppressed the serum concentrations of total immunoglobulin E (IgE) and OVA-specific IgG1 in OVA-induced asthmatic mice, and alleviated the pathological changes of lung tissues, which was reversed by rSerpinA3n injection (P < 0.05). Besides, WT + OVA group showed more severe in collagen deposition in lung tissues than SerpinA3n + OVA group with increased expression of matrix metallopeptidase-2 (MMP-2), MMP-9, Eotaxin-1, Interleukin 5 (IL-5), IL-13 and IL-4 in lung tissues and deceased IL-10 and Interferon-gamma (IFN-γ) (P < 0.05). Nevertheless, the ameliorating effects of SerpinA3n knockout on OVA-induced asthmatic mice can be reversed by rSerpinA3n.
SerpinA3n knockout can attenuate airway hyper-reactivity, mitigate inflammatory responses and reduce collagen deposition in lung tissues of neonatal mice with asthma.
研究丝氨酸蛋白酶抑制剂 3n（SerpinA3n）在新生鼠哮喘模型中的作用。
本研究采用新生鼠卵清蛋白（OVA）致敏哮喘模型。野生型（WT）和 SerpinA3n 小鼠随机分为 WT/SerpinA3n+生理盐水、WT/SerpinA3n+OVA、WT/SerpinA3n+OVA+rSerpinA3n（重组鼠 SerpinA3n 蛋白）和 WT/SerpinA3n+OVA+DEX（地塞米松，阳性对照）组，随后进行苏木精-伊红（HE）染色、马松三色染色、Sircol 可溶性胶原测定、实时定量聚合酶链反应（qRT-PCR）、Western Blot 和酶联免疫吸附试验（ELISA）。
OVA 诱导的新生鼠出现气道高反应性，支气管肺泡灌洗液（BALF）中总细胞、嗜酸性粒细胞、淋巴细胞和中性粒细胞增加，WT+OVA+rSerpinA3n 组增加更明显（P<0.05）。SerpinA3n 抑制 OVA 诱导的哮喘小鼠血清总免疫球蛋白 E（IgE）和 OVA 特异性 IgG1 浓度，并减轻肺组织病理变化，rSerpinA3n 注射可逆转上述变化（P<0.05）。此外，与 SerpinA3n+OVA 组相比，WT+OVA 组肺组织胶原沉积更严重，肺组织基质金属蛋白酶-2（MMP-2）、MMP-9、嗜酸性粒细胞趋化因子-1（Eotaxin-1）、白细胞介素 5（IL-5）、白细胞介素 13（IL-13）和白细胞介素 4（IL-4）表达增加，IL-10 和干扰素-γ（IFN-γ）表达减少（P<0.05）。然而，rSerpinA3n 可逆转 SerpinA3n 缺失对 OVA 诱导的哮喘小鼠的改善作用。
SerpinA3n 缺失可减轻新生鼠哮喘的气道高反应性，减轻炎症反应，减少肺组织胶原沉积。
