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Development of a minimal invasive and controllable murine model to study polymicrobial abdominal sepsis
Frontiers in Life Science Pub Date : 2021-04-08 , DOI: 10.1080/26895293.2021.1909663
Folkert Steinhagen 1 , Tobias Hilbert 1 , Nina Cramer 1 , Sebastian Senzig 1 , Marijo Parcina 2 , Christian Bode 1 , Olaf Boehm 1 , Stilla Frede 1 , Sven Klaschik 1
Affiliation  

Sepsis, a life-threatening organ dysfunction, continues to cause considerable morbidity. Reliable animal models to evaluate therapeutic options are urgently required, however, some of the most established ones are technically challenging. We herein present a murine model of abdominal sepsis based on the intraperitoneal (i.p.) injection of a defined inoculum of stool specimens (IPSI). Fecal bacterial compositions of male C57BL/6N mice were used for experiments. Dilutions of suspended stool (1:3, 1:6, 1:9) were injected i.p. into recipient mice. Clinical symptoms, cytokine expression, and mortality were assessed up to 48 h following IPSI. Storage at 4°C for 72 h exerted only minimal effect on bacterial composition, while deep freezing substantially impacted bacterial viability. After 9 h following IPSI, a dose-dependent, significant increase in clinical score was visible in all stool-injected mice. The same was observed for expression levels of pro-inflammatory cytokines IL-6 and CCL-2. Mortality rate of septic mice ranged from ∼30% (1:9) to 100% (1:3) within 48 h, depended on the dilution of stool inoculum. The IPSI model ensures experimental stability while mimicking a pathophysiological relevant stimulus similar to other established models. Characterization of microbial composition, minimal invasiveness and easy technical handling allow a good reproducibility and disease severity can be titrated.



中文翻译:

开发微创和可控制的小鼠模型以研究多菌性腹部脓毒症

败血症是一种威胁生命的器官功能障碍,继续引起相当大的发病率。迫切需要可靠的动物模型来评估治疗方案,但是,一些最成熟的动物模型在技术上具有挑战性。我们在此提出一种基于腹膜内(ip)注射的粪便标本接种物(IPSI)的腹部脓毒症小鼠模型。将雄性C57BL / 6N小鼠的粪便细菌组成用于实验。将悬浮粪便的稀释液(1:3、1:6、1:9)经腹膜内注射到受体小鼠体内。在IPSI后48小时内评估临床症状,细胞因子表达和死亡率。在4°C下储存72小时对细菌组成的影响很小,而深度冷冻则显着影响细菌的生存能力。IPSI后9小时后,出现剂量依赖性,在所有粪便注射的小鼠中,临床评分均显着增加。促炎细胞因子IL-6和CCL-2的表达水平也观察到相同。化脓小鼠的死亡率在48小时内约为30%(1:9)至100%(1:3),这取决于粪便接种物的稀释度。IPSI模型可确保实验稳定性,同时可模仿与其他已建立模型类似的病理生理相关刺激。微生物成分的表征,最小的侵袭性和易于技术处理使重现性良好,并且可以确定疾病的严重程度。IPSI模型可确保实验稳定性,同时可模仿与其他已建立模型类似的病理生理相关刺激。微生物成分的表征,最小的侵袭性和易于技术处理使重现性良好,并且可以确定疾病的严重程度。IPSI模型可确保实验稳定性,同时可模仿与其他已建立模型类似的病理生理相关刺激。微生物成分的表征,最小的侵袭性和易于技术处理使重现性良好,并且可以确定疾病的严重程度。

更新日期:2021-04-08
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