Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Kazunobu Yamaguchi, C. Shindoh, M. Miura
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Abstract

Objective: We investigated diaphragm contractile and inflammatory properties of mice with OVA sensitization and challenge. Methods: BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection at 0 and 7 days, and challenged with aerosolized OVA on 21, 22, and 23 days (O/O group). Budesonide/Formoterol combination was inhaled on days 21, 22, and 23 before OVA challenge on those same days (O/OC group). Control mice were sensitized and challenged with an aerosolized saline (O-group). The diaphragm contractile and inflammatory properties were measured on day 24. NOS activity in the diaphragm muscle was evaluated by NADPH diaphorase staining. IL-4 and IL-13 levels of BALF, as well as lung tissue and diaphragm muscle homogenates were measured by ELISA. Results: Force-frequency (F/f) curves of O/O and O/OC shifted downward in comparison with O- (p<0.05). NADPH diaphorase staining results of O/O and O/OC showed a significantly higher density compared with O-. The IL-4 level of diaphragm muscle homogenates increased significantly in the O/O compared with the O- and O/OC. Conclusions: OVA sensitization and challenge decreased diaphragm muscle contraction, increased NOS activity, IL-4 levels of diaphragm in a mouse model. Budesonide/Formoterol combination could protect diaphragm muscle weakness and inflammation. According to the traditional concept of the contemporary Immunology, neither autoimmune diseases nor allergic diseases can be cured completely. Nevertheless, a fortunate coincidence led me to discovery of a novel concept that eliminations of the causes of these diseases are possible. In other words, combinations of pathogenic antibodies with responsible cells, namely, cytolytic T lymphocytes in cases of autoimmune diseases and mast cells in cases of allergic diseases, can be decomposed by replacing the pathogenic antibodies with non-specific antibodies. In more detail, intradermal injections with a non-specific antigen preparation induce production of non-specific antibodies in the body of the patient. Repetitions of the injections bring about an accumulation of them. Accumulated non-specific antibodies will occupy most of the receptors on the surface of responsible cells. When the accumulation reaches the sufficient level, virtually no pathogenic antibodies would remain on the receptors. That is, no causes of the diseases remain. Naturally, where there is no cause, there is no disease. Details are demonstrated elsewhere.
卵清蛋白致变应性气道炎症小鼠模型膈肌收缩减少
目的:研究OVA致敏和激射小鼠膈肌的收缩和炎症特性。方法:BALB/c小鼠分别于第0、7天腹腔注射OVA致敏,第21、22、23天雾化注射OVA致敏(O/O组)。布地奈德/福莫特罗联合用药于第21、22、23天吸入,并于当日攻卵前(O/OC组)。对照组小鼠被雾化生理盐水致敏和刺激(o组)。第24天测量膈肌收缩和炎症特性。采用NADPH法测定膈肌NOS活性。ELISA法检测大鼠BALF、肺组织和膈肌匀浆中IL-4、IL-13水平。结果:O/O和O/OC的力频(F/ F)曲线较O-下降(p<0.05)。O/O和O/OC的NADPH脱氢酶染色结果显示,与O-相比,O/O和O/OC的密度明显更高。与O-和O/OC组相比,O/O组膈肌匀浆IL-4水平显著升高。结论:OVA致敏和刺激可降低小鼠膈肌收缩,提高膈肌NOS活性和IL-4水平。布地奈德/福莫特罗联用对膈肌无力和炎症有保护作用。按照当代免疫学的传统观念,无论是自身免疫性疾病还是过敏性疾病,都不能完全治愈。然而,一个幸运的巧合使我发现了一个新的概念,即消除这些疾病的原因是可能的。换句话说,病原性抗体与负责细胞的组合,即自身免疫性疾病中的细胞溶解性T淋巴细胞和过敏性疾病中的肥大细胞,可以通过用非特异性抗体代替病原性抗体来分解。更详细地说,皮内注射非特异性抗原制剂可诱导患者体内产生非特异性抗体。反复注射会使它们积累起来。积累的非特异性抗体会占据负责细胞表面的大部分受体。当积累达到足够的水平时,几乎没有致病抗体会留在受体上。也就是说,这些疾病的病因已不复存在。自然,没有病因就没有疾病。细节在其他地方展示。
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