| 周宁娟,徐海军,金巧艳,张 娟,李秋红,吴海霞,苏 慧,孙 新.小鼠胰岛素抵抗哮喘模型的建立与评估[J].,2018,(7):1259-1263 |
| 小鼠胰岛素抵抗哮喘模型的建立与评估 |
| Establishment of Mouse Insulin Resistance Asthma Model and Its Evaluation |
| 投稿时间：2017-06-30 修订日期：2017-07-25 |
| DOI：10.13241/j.cnki.pmb.2018.07.012 |
| 中文关键词: 胰岛素抵抗 哮喘 动物模型 |
| 英文关键词: Insulin resistance Asthma Mouse model |
| 基金项目:国家自然科学基金项目（81670449；31371151；31271219） |
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| 中文摘要: |
| 摘要 目的：探讨小鼠胰岛素抵抗哮喘模型的建立方法，并进行评估。方法：C57BL/6J小鼠随机分为4组：正常对照组（HC）、哮喘组(NIRA)均给予普通饲料喂养；胰岛素抵抗组IRNA)、胰岛素抵抗+哮喘组(IRA)均给予高脂饲料（D12492）喂养。每周称重，第6-14周，每周检测各组小鼠空腹血糖(FPG)、空腹血清胰岛素(FINS)水平，计算稳态模型胰岛素抵抗评价指数(HOMA-IR)评估胰岛素抵抗程度；小鼠胰岛素抵抗模型建立成功后在其基础上诱导哮喘模型，NIRA组和IRA组小鼠给予卵清蛋白(OVA)致敏、激发； HC组和IRNA组小鼠给予生理盐水作为对照，末次激发24后，制作肺病理切片，计数肺泡灌洗液（BALF）中白细胞总数及分类，检测血清和BALF中相关炎性因子的水平，比较各组小鼠胰岛素抵抗指数与哮喘评价指标，评估模型。结果：(1)第9周末，IRNA组、IRA组小鼠的HOMA-IR值均＞2.5，表明胰岛素抵抗小鼠模型建立成功；(2)肺组织病理切片中，HC组、IRNA组小鼠肺组织无炎症改变，NIRA组、IRA组炎细胞浸润明显，尤以IRA组更甚。(3)与HC组比较，NIRA组(P< 0.01)、IRA组(P< 0.01)BALF中白细胞总数、嗜酸性粒细胞比例明显增高；(4)血清中抗OVA 特异性IgE( P＜0.01) 和IgG1( P＜0.05)水平显著升高；(5)血清和BALF中IL-4（P<0.01）、IL-17（P<0.05）的水平明显升高，且IRA组(P<0.05)明显高于NIRA组；IFN-γ（P<0.05）的水平明显降低，且IRA组（P<0.05）明显低于NIRA组。结论：用高脂饲料喂养C57BL/6J小鼠9周，可建立稳定的胰岛素抵抗模型，从第10周开始用OVA致敏、激发诱发哮喘，可成功建立稳定的胰岛素抵抗哮喘小鼠模型，为进一步研究胰岛素抵抗与哮喘相关机制奠定基础。 |
| 英文摘要: |
| ABSTRACT Objective: We are aimed to establish a model of insulin resistance asthma, and to evaluate its. Methods: C57BL/6J mice were randomly divided into four experimental groups. The four groups of mice were treated as follow: The healthy control group（HC） and non-insulin resistance asthmatic group（NIRA）received a standard chow diet. The insulin resistance non-asthmatic group（IRNA）and insulin resistance asthmatic group（IRA）were fed with a high-fat diet（D12492）. All animals were weighed peer week. From 6-14 weeks, the fasting blood-glucose（FPG）and fasting insulin（FINS）were tested every week. Systemic insulin sensitivity was assessed by homoeostasis model assessment-estimated insulin resistance（HOMA-IR）index. After insulin resistance mouse model was successfully established, NIRA group and IRA group received ovalbumin（OVA）orally and intraperitoneally to induce allergic asthma, HC group and IRNA group were treated with equal normal saline（NS）as control. 24 hours after final challenge, lung tissue was prepared for morpho- metrical lung analysis and broncho alveolar lavage fluid (BALF) was performed. Leukocyte and its subgroup populations in the bron- choalveolar lavage fluidwere counted, and levels of associated inflammatory factors were detected.Whether the model of insulin resis- tance associated asthma was successfully established was assessed by comparing insulin resistance index and severity of asthma of each group. Results: (1)The average of HOMA-IR of IRNA group and IRA group was higher than 2.5. The result demonstrated that the insulin resistance mouse model was successfully established. (2)There was no appreciableinflammatory cells infiltration in lungs of HC group and IRNA group. However, both NIRA group and IRA group showed significant increased inflammatory infiltration, while IRA group exhibited higher numbers of inflammatory cells compared to NIRA group.(3) The significant increasecanobserved in the number oftotal inflammatory cells and eosinophilsin NIRA group(P<0.01) and IRA group(P<0.01) compared to HC group. (4)OVA-specific IgE(P<0.01)/IgG1(P<0.05) significantly elevated in NIRA group and IRA group but not HC group. (5)Th2 cytokinesin the BALF(IL-4, IL-17) and serum(IL-4, IL-17) were significantly increased in NIRA group(P<0.05) and IRA group(P<0.05), especially in IRA group. However, the level of IFN-γ decreased in NIRA group(P<0.05) and IRA group(P<0.05), especially in IRA group. Conclusion: Stable insulin resistance mouse model could be established by feeding C57BL/6J mice with high-fat diet for 9 weeks, from the 10thweek, it is available to establish stable insulin resistance asthma model by induce asthma by the time stable insulin resistance mouse model is established, and for the further study of mechanism of insulin resistance associated with asthma. |
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