CAJ | 학술논문

目的：建立卵蛋白（ OVA）致敏激发后，在挪威褐鼠无创且清醒的状态下，可观察和记录到过敏性哮喘发作全过程（速发相和迟发相）的动物模型。方法66只挪威褐鼠按致敏液[OVA和Al（OH）3]不同平均分为11组，单纯注射OVA的4组（0.01、0.1、1.0和10.0 mg／只）；OVA混合Al（OH）3干粉的5组（0.1＋100、1.0＋100、10.0＋100、1.0＋52和1.0＋4 mg／只）；OVA混合Al（OH）3胶体的1组（10.0＋4 mg／只）；正常对照组1组。10个致敏组分别于第0天和第5天背部皮下2点注射相应致敏液，每点注射0.2 mL，正常对照组注射等量生理盐水。在第37天雾化吸入5％OVA激发10 min。然后立即放入体积描记器中连续记录16 h呼气相延长参数（ penh）值。采集第0、7、14、21、28、35、38天血清，ELISA法检测特异性IgE含量。 HE染色观察肺病理变化。结果除单纯注射OVA 0.01 mg组外，其他各组大鼠血清特异性IgE含量均比正常对照组显著升高（ P＜0.05），且在致敏1周后IgE开始大量产生，直到第5周均呈持续增长趋势。观察到了哮喘发作的速发和迟发双相气道反应，其特点表现在Penh值的显著增高，且与正常对照组相比，模型组（以OVA 10.0&Al（OH）3100、OVA 10.0& Al（OH）3 gel 4组为例）的速发相／迟发相峰值、面积均显著增大（P＜0.05）。模型组（以OVA 10.0&Al（OH）3100组为例）有以气道周围嗜酸性粒细胞浸润为主的炎症表现。结论成功建立了无创、清醒状态下挪威褐鼠过敏性哮喘发作全程记录模型。
목적：건립란단백（ OVA）치민격발후，재나위갈서무창차청성적상태하，가관찰화기록도과민성효천발작전과정（속발상화지발상）적동물모형。방법66지나위갈서안치민액[OVA화Al（OH）3]불동평균분위11조，단순주사OVA적4조（0.01、0.1、1.0화10.0 mg／지）；OVA혼합Al（OH）3간분적5조（0.1＋100、1.0＋100、10.0＋100、1.0＋52화1.0＋4 mg／지）；OVA혼합Al（OH）3효체적1조（10.0＋4 mg／지）；정상대조조1조。10개치민조분별우제0천화제5천배부피하2점주사상응치민액，매점주사0.2 mL，정상대조조주사등량생리염수。재제37천무화흡입5％OVA격발10 min。연후립즉방입체적묘기기중련속기록16 h호기상연장삼수（ penh）치。채집제0、7、14、21、28、35、38천혈청，ELISA법검측특이성IgE함량。 HE염색관찰폐병리변화。결과제단순주사OVA 0.01 mg조외，기타각조대서혈청특이성IgE함량균비정상대조조현저승고（ P＜0.05），차재치민1주후IgE개시대양산생，직도제5주균정지속증장추세。관찰도료효천발작적속발화지발쌍상기도반응，기특점표현재Penh치적현저증고，차여정상대조조상비，모형조（이OVA 10.0&Al（OH）3100、OVA 10.0& Al（OH）3 gel 4조위례）적속발상／지발상봉치、면적균현저증대（P＜0.05）。모형조（이OVA 10.0&Al（OH）3100조위례）유이기도주위기산성립세포침윤위주적염증표현。결론성공건립료무창、청성상태하나위갈서과민성효천발작전정기록모형。
Objective To establish an animal model in which both early-phase asthmatic response (EAR) and late-phase asthmatic response ( LAR) can be observed after sensitization and subsequent inhalation challenge with ovalbumin ( OVA) .Animals were conscious with no narcotic used, unrestricted, and fed ad libitum.Methods Sixty-six SPF 6-8-week old male Brown Norway rats were divided into eleven equal groups.All groups of rats except normal control group were injected subcutaneously with 0.4 mL (sc in back, 2 sites, 0.2 mL/site) OVA or OVA +Al(OH)3 solution on day 0 and day 5.Four groups were given OVA only at the dose of 0.01, 0.1, 1.0 or 10.0 mg/rat, five groups were given OVA +Al(OH)3 powder at the dose of 0.1+100, 1.0+100, 10.0+100, 1.0+52 and 1.0+4 mg/rat, one group was given OVA+Al(OH)3 gel at the dose of 10.0+4 mg/rat.Normal control group was injected subcutaneously with the same volume of saline.All the groups were challenged for 10 minutes with 5 mL 5%OVA aerosol on day 37.Enhanced pause ( Penh) was recorded for 16 hours in a whole-body plethysmography system after challenge.Specific IgE of the serum samples on day 0, 7, 14, 21, 28, 35, 38 were measured by ELISA.Pulmonary pathological changes were observed using HE staining.Results Compared with the normal control group, immunized rats except the group given 0.01 mg OVA produced specific IgE (P<0.05), and the content of IgE grew sharply after 7 days, and always kept growing until 5 weeks.The whole course of asthma exacerbation was recorded successfully.The rats developed EAR and/or LAR within 16 hours following OVA challenge. Especially the groups injected with 10 mg OVA and 100 mg Al(OH)3 or 4 mg Al(OH)3 gel showed steady pattern of biphasic airway responses and their EAR or LAR peak, and the area under the curve were increased significantly compared with those of the normal control group (P<0.05).Inflammation characterized by eosinophil infiltration was observed in the rat lung of model group (OVA 10.0 & Al(OH)3100 group as a representative case).Conclusions In this work we successfully developed a new model using conscious rats, and the whole time course of asthma exacerbation in this model can be observed after OVA challenge.This model may become a useful tool for further asthma research.