Background: Sepsis is one of the most dangerous syndromes, has extremely high mortality, and is caused by the body’s extreme responses to an infection. The pathogenesis of sepsis is very complex and remains largely unknown and thus the treatments for sepsis are limited. Here, we evaluated the treatment results of two potential drugs, glutamine and ulinastatin, on sepsis.
Methods: CLP rat model was used to study sepsis. Gastrostomy was performed to deliver the drugs. Flow cytometry was employed to measure CD4 and CD8 levels. May–Grünwald–Giemsa staining was used to count the numbers of monocytes and neutrophils in the blood. ELISA assay was performed to assess the levels of PCT, IL-6, TNFα, and IL-1β.
Results: Sepsis was successfully induced with the standard CLP rat model. Both glutamine and ulinastatin treatments greatly improved the outcomes of sepsis, but the combination of both treatments had the maximum therapeutic effect. Mechanistically, PCT, IL-6, TNFα, and IL-1β levels were significantly diminished following glutamine and ulinastatin treatments, suggesting an inhibition of inflammatory responses. Further, CD4 and CD4/CD8 ratio, and the numbers of monocytes and neutrophils were greatly up-regulated by glutamine and ulinastatin, indicating an enhanced immunity.
Conclusion: Glutamine and ulinastatin treatments largely mitigate sepsis shock by suppressing the inflammatory responses of the body and strengthening the immune system. Combination of these two drugs could serve as a potential treatment for sepsis.



中文翻译：

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谷氨酰胺和乌司他丁治疗的结合极大地改善了脓毒症的结果。

背景：脓毒症是最危险的综合征之一，死亡率极高，是由身体对感染的极端反应引起的。脓毒症的发病机制非常复杂并且在很大程度上仍然未知，因此脓毒症的治疗是有限的。在这里，我们评估了两种潜在药物谷氨酰胺和乌司他丁对脓毒症的治疗效果。
方法：采用CLP大鼠模型研究脓毒症。进行胃造口术以输送药物。流式细胞仪用于测量 CD4 和 CD8 水平。May-Grünwald-Giemsa 染色用于计算血液中单核细胞和中性粒细胞的数量。进行ELISA测定以评估PCT、IL-6、TNFα和IL-1β的水平。
结果：用标准 CLP 大鼠模型成功诱导脓毒症。谷氨酰胺和乌司他丁治疗都极大地改善了脓毒症的结果，但两种治疗的组合具有最大的治疗效果。机制上，PCT、IL-6、TNFα 和 IL-1β 水平在谷氨酰胺和乌司他丁治疗后显着降低，表明炎症反应受到抑制。此外，CD4 和 CD4/CD8 比值以及单核细胞和中性粒细胞的数量被谷氨酰胺和乌司他丁大大上调，表明免疫力增强。
结论：谷氨酰胺和乌司他丁治疗通过抑制身体的炎症反应和增强免疫系统在很大程度上减轻了脓毒症休克。这两种药物的组合可以作为败血症的潜在治疗方法。