脓毒症时发生炎症过度,尤其是在早期阶段,对脓毒症有积极和消极的影响.以前,我们证明了NF-κB抑制剂的新概念,基于外泌体的超抑制因子IκBα(Exo-srIκB)递送,对脓毒症有有益的作用.这里,我们使用动物多微生物腹腔感染模型进一步研究了Exo-srIκB在脓毒症不同严重程度和阶段的治疗效果.我们使用了粪便浆液多微生物败血症的大鼠模型。首先,我们根据严重程度确定了Exo-srIκB对脓毒症的生存影响。我们使用两种不同严重程度的动物败血症模型。严重模型的死亡率超过50%。轻度/中度模型的死亡率低于30%。第二,我们在不同的时间点施用Exo-srIκB(1小时,6h,和粪便浆液给药后24小时),以确定Exo-srIκB在脓毒症不同阶段的治疗效果。最后,我们确定了Exo-srIκB对细胞因子产生的影响,动脉血气,电解质,和乳酸。脓毒症后6小时给予Exo-srIκB时,严重脓毒症模型的生存增加具有统计学意义。当施用Exo-srIκB时,肾脏中的白细胞介素6和白细胞介素10显着降低。实验室数据显示乳酸,葡萄糖,NF-κB抑制剂组的钾水平显着降低。总之,当在严重脓毒症模型中粪便浆液给药后6小时给药时,Exo-srIκB表现出有益的治疗效果。
Hyperinflammation occurs in sepsis, especially in the early phase, and it could have both positive and negative effects on sepsis. Previously, we showed that a new concept of NF-κB inhibitor, exosome-based super-repressor IκBα (Exo-srIκB) delivery, has a beneficial effect on sepsis. Here, we further investigate the therapeutic effects of Exo-srIκB at different severities and phases of sepsis using an animal polymicrobial intra-abdominal infection model. We used a rat model of fecal slurry polymicrobial sepsis. First, we determined the survival effects of Exo-srIκB on sepsis according to the severity. We used two different severities of the animal sepsis model. The severe model had a mortality rate of over 50%. The mild/moderate model had a less than 30% mortality rate. Second, we administered the Exo-srIκB at various time points (1 h, 6 h, and 24 h after fecal slurry administration) to determine the therapeutic effect of Exo-srIκB at different phases of sepsis. Lastly, we determined the effects of the Exo-srIκB on cytokine production, arterial blood gas, electrolyte, and lactate. The survival gain was statistically significant in the severe sepsis model when Exo-srIκB was administered 6 h after sepsis. Interleukin 6 and interleukin-10 were significantly decreased in the kidney when administered with Exo-srIκB. The laboratory data showed that lactate, glucose, and potassium levels were significantly lowered in the NF-κB inhibitor group. In conclusion, Exo-srIκB exhibited a beneficial therapeutic effect when administered 6 h post fecal slurry administration in a severe sepsis model.