A Versatile New Model of Chemically Induced Chronic Colitis Using an Outbred Murine Strain.
A Versatile New Model of Chemically Induced Chronic Colitis Using an Outbred Murine Strain.
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DOI：
10.3389/fmicb.2018.00565
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发表时间：
2018
影响因子：
5.2
通讯作者：
Martín R
中科院分区：
文献类型：
--
作者：
Barone M;Chain F;Sokol H;Brigidi P;Bermúdez-Humarán LG;Langella P;Martín R
小鼠结肠炎模型是理解肠道稳态和炎症的重要工具。然而，目前大多数模型利用高度近交系小鼠，并且通常仅采用一种性别以限制偏倚。这种有针对性的方法本身就是有偏见的，这意味着鼠科动物的遗传多样性和与性别相关的差异被忽视了，这使得将研究结果扩展到高度异质性的人类更加困难。此外，大多数模型不检查结肠炎的慢性形式，考虑到炎症性肠病（IBD）的慢性性质，这是一个重要的事实。在这里，我们试图通过解决这三个问题来创建一个更现实的小鼠结肠炎模型。在远交系小鼠（RjOrl：SWISS [CD-1]）中使用化学诱导的慢性结肠炎症，我们（i）模拟了疾病的复发性质，（ii）更好地代表了正常的遗传变异性，（iii）使用了雌性和雄性小鼠。结肠炎由直肠内给予二硝基苯磺酸（DNBS）诱导。在恢复期后和对小鼠实施安乐死前3天，通过第二次施用DNBS重新激活结肠炎。方案持续时间为24天。结肠炎的严重程度通过体重、肉眼评分和组织学评分进行评估。还对髓过氧化物酶（MPO）活性、细胞因子水平和淋巴细胞数量进行了表征。我们的研究结果表明，DNBS的直肠内给药有效地导致结肠炎的雌性和雄性CD-1小鼠以剂量依赖性的方式，反映了身体质量的损失，宏观评分和组织学评分。此外，结肠细胞因子水平和肠系膜淋巴结特征表明该模型涉及免疫系统激活。虽然有些变量是性别特异性的，但大多数结果支持在模型中包括女性和男性。我们的最终目标是让研究人员可以使用这种模型来测试候选抗炎药，例如经典或下一代益生菌;我们还希望结果更容易转移到人体试验中。
Murine colitis models are crucial tools for understanding intestinal homeostasis and inflammation. However, most current models utilize a highly inbred strain of mice, and often only one sex is employed to limit bias. This targeted approach, which in itself is biased, means that murine genetic diversity and sex-related differences are ignored, making it even more difficult to extend findings to humans, who are highly heterogeneous. Furthermore, most models do not examine the chronic form of colitis, an important fact taking into account the chronic nature of the inflammatory bowel diseases (IBD). Here, we attempted to create a more realistic murine colitis model by addressing these three issues. Using chemically induced chronic colon inflammation in an outbred strain of mice (RjOrl:SWISS [CD-1]), we (i) mimicked the relapsing nature of the disease, (ii) better represented normal genetic variability, and (iii) employed both female and male mice. Colitis was induced by intrarectal administration of dinitrobenzene sulfonic acid (DNBS). After a recovery period and 3 days before the mice were euthanized, colitis was reactivated by a second administration of DNBS. Protocol length was 24 days. Colitis severity was assessed using body mass, macroscopic scores, and histological scores. Myeloperoxidase (MPO) activity, cytokine levels, and lymphocyte populations were also characterized. Our results show that the intrarectal administration of DNBS effectively causes colitis in both female and male CD-1 mice in a dose-dependent manner, as reflected by loss of body mass, macroscopic scores and histological scores. Furthermore, colon cytokine levels and mesenteric lymph node characteristics indicate that this model involves immune system activation. Although some variables were sex-specific, most of the results support including both females and males in the model. Our ultimate goal is to make this model available to researchers for testing candidate anti-inflammatory agents, such as classical or next-generation probiotics; we also aim for the results to be more easily transferrable to human trials.
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影响因子：
13.2
作者：
Jin, Wei;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
3.1
作者：
Gerlach, Katharina;McKenzie, Andrew N.;Weigmann, Benno
通讯作者：
Weigmann, Benno
DOI：
10.1084/jem.189.8.1169
发表时间：
1999-04-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dohi T;Fujihashi K;Rennert PD;Iwatani K;Kiyono H;McGhee JR
通讯作者：
McGhee JR
影响因子：
29.4
作者：
Schreiber, S;Fedorak, RN;Hanauer, SB
通讯作者：
Hanauer, SB
DOI：
10.1126/science.aad9382
发表时间：
2016-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Pamer EG
通讯作者：
Pamer EG