Yang Xudong, Sun Qingzhu, Asim M B Raza, Jiang Xiaogang, Zhong Bo, Shahzad Muhammad, Zhang Fujun, Han Yan, Lu Shemin
Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of Medicine, Xir'an, Shaanxi 710061, PR China.
J Asthma. 2010 Mar;47(2):135-44. doi: 10.3109/02770900903483808.
Nitric oxide (NO) is considered as a hallmark for allergic airway inflammation in asthmatics and animal models. But the correlation between NO and antigen-induced pulmonary inflammation (AIPI), a rat model for asthma, in varying genetic background population has not been completely understood.
The objective in this study is to observe the different responsiveness to AIPI in two commonly used inbred rat strains and verify the correlation between NO from different sources and pathological parameters of AIPI by using Dark Agouti (DA), E3, F1 (E3 x DA), and F2 rat populations.
AIPI was induced by systemically immunizing and intranasally challenging E3, DA, F1 (DA x E3), and F2 rats with ovalbumin (OVA). Pathological changes and mucus secretion in lungs were observed after hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining, whereas eosinophils in bronchoalveolar lavage fluid (BALF) were counted after Giemsa staining. Delayed-type hyperresponsiveness was determined by subcutaneous injection of OVA in ear. Total immunoglobulin E (IgE) and OVA-specific IgG1 were detected with enzyme-linked immunosorbent assay (ELISA). NO concentration was measured by the Griess method.
DA rats were unresponsive to OVA treatment, whereas E3 rats were susceptible to AIPI. F1 rats manifested the same responsiveness to OVA treatment as DA rats, and individual F2 rats showed the variable severity of AIPI. NO concentration in BALF and serum was significantly elevated in E3 rats but not in DA and F1 rats after OVA treatment. In F2 rats, NO concentration in serum was positively correlated with eosinophils in BALF, total IgE, and pathological scores, whereas NO concentration in BALF correlated only with eosinophils in BALF and total IgE.
DA and F1 rats are resistant, whereas E3 rats are sensitive, to AIPI. NO in serum can represent the severity of allergic inflammation and pathological changes in lungs in F2 population.
一氧化氮（NO）被认为是哮喘患者及动物模型中过敏性气道炎症的一个标志。但在不同遗传背景群体中，NO与抗原诱导的肺部炎症（AIPI，一种哮喘大鼠模型）之间的相关性尚未完全明确。
本研究的目的是观察两种常用近交系大鼠对AIPI的不同反应性，并通过使用黑褐大鼠（DA）、E3、F1（E3×DA）和F2大鼠群体，验证不同来源的NO与AIPI病理参数之间的相关性。
通过用卵清蛋白（OVA）对E3、DA、F1（DA×E3）和F2大鼠进行全身免疫和鼻内激发来诱导AIPI。苏木精-伊红（HE）和过碘酸希夫（PAS）染色后观察肺组织的病理变化和黏液分泌情况，吉姆萨染色后对支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞进行计数。通过在耳部皮下注射OVA来测定迟发型超敏反应。采用酶联免疫吸附测定（ELISA）检测总免疫球蛋白E（IgE）和OVA特异性IgG1。用格里斯法测定NO浓度。
DA大鼠对OVA处理无反应，而E3大鼠易患AIPI。F1大鼠对OVA处理的反应性与DA大鼠相同，且F2大鼠个体表现出AIPI严重程度的差异。OVA处理后，E3大鼠BALF和血清中的NO浓度显著升高，而DA和F1大鼠则未升高。在F2大鼠中，血清中的NO浓度与BALF中的嗜酸性粒细胞、总IgE及病理评分呈正相关，而BALF中的NO浓度仅与BALF中的嗜酸性粒细胞和总IgE相关。
DA和F1大鼠对AIPI具有抗性，而E3大鼠敏感。血清中的NO可代表F2群体中过敏性炎症的严重程度及肺部的病理变化。
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