Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Science and Technology Experiment Center of Cangzhou Medical College, Cangzhou 061001, China.
Int Immunopharmacol. 2018 Sep;62:67-76. doi: 10.1016/j.intimp.2018.05.031. Epub 2018 Jul 5.
Immunosuppression is an important mechanism for the development of sepsis pathology, and is the key to the high mortality of sepsis. However, patients appear to be immunocompromised before sepsis onset due to lack of enough attention. Present sepsis models cannot fully mimic the onset of sepsis in patients. Hence, effective treatments in animal experiments could not be transformed into clinical application. In the present study, we improved the animal model of sepsis and used cyclosporine A immunosuppressive mice to make it closer to immune status before the onset of sepsis, followed by the intraperitoneal injection of Escherichia coli (E. coli) CMCC (B) 44,102 standard strain to produce the immunocompromised sepsis model. This trial systematically evaluates the new immunosuppressive sepsis model. Compared with routine sepsis models, the release of inflammatory factors in the new sepsis model was insufficient, blood bacteria were more cultured, diffuse intravascular coagulation (DIC) was more severe, lung, liver and kidney damage were heavier, and mortality rate was higher. In conclusion, the new sepsis model can mimic the patient's pre-onset immunocompromised state, is suitable for the development and evaluation of new methods of sepsis, and solves the controversy of sepsis treatment, providing new ideas and direction.
免疫抑制是脓毒症发病机制中的一个重要机制,也是脓毒症高死亡率的关键。然而,由于缺乏足够的重视,患者在脓毒症发作前似乎已经免疫功能低下。目前的脓毒症模型不能完全模拟患者脓毒症的发病过程。因此,动物实验中的有效治疗方法无法转化为临床应用。在本研究中,我们改进了脓毒症动物模型,使用环孢素 A 免疫抑制小鼠使其更接近脓毒症发病前的免疫状态,然后腹腔内注射大肠埃希菌(Escherichia coli)CMCC(B)44,102 标准株,产生免疫功能低下的脓毒症模型。本试验系统地评价了新的免疫抑制性脓毒症模型。与常规脓毒症模型相比,新型脓毒症模型中炎症因子的释放不足,血液细菌培养更多,弥漫性血管内凝血(DIC)更严重,肺、肝、肾损伤更严重,死亡率更高。总之,新型脓毒症模型能够模拟患者发病前的免疫功能低下状态,适合脓毒症新治疗方法的开发和评价,解决了脓毒症治疗的争议,为其提供了新的思路和方向。