Application of intervention 14-3-3 in treatment of sepsis

A sepsis and drug technology, applied in the application field of intervention 14-3-3 in the treatment of sepsis, can solve the problems of unclear activation mechanism, lack of early effective drug treatment, high mortality, and achieve slowing down. The effect of lung pathological damage, slowing down inflammatory factor storm and improving survival rate

Active Publication Date: 2020-06-12
THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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  • Claims
  • Application Information

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Problems solved by technology

[0003] Studies have shown that the NLRP3 inflammasome promotes the maturation and secretion of IL-1β, which plays an important role in the development of sepsis, but the specific mechanism of its activation is still unclear
Although various countries have devoted a lot of manpower, material and financial resources to the treatment of sepsis, the mortality rate is still high. One of the main reasons is the lack of early and effective drug treatment.

Method used

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  • Application of intervention 14-3-3 in treatment of sepsis
  • Application of intervention 14-3-3 in treatment of sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 114-3-3

[0021] Example 1 Study on 14-3-3 myeloid cell-deficient mice

[0022] Using 4-6 weeks of SPF grade female C57BL / 6 mice, WT mice and 14-3-3 gene-deficient mice were used to establish cecal ligation sepsis (CLP) models. Observe and record the mouse survival rate, the results are as follows: figure 1 As shown in A.

[0023] 4-6 weeks old SPF grade female C57BL / 6 mice were used to construct a mouse cecal ligation sepsis model (construct a cecal ligation sepsis model mouse according to the conventional method in the field). Take mouse lung and peritoneal lavage fluid. The lung lobules were fixed with 4% paraformaldehyde, the lung tissue sections were stained with H&E, and observed under a microscope, the results were as follows figure 1 Shown in B.

[0024] The remaining lung tissue was ground, filtered, and stained with specific flow cytometry antibodies together with peritoneal lavage fluid to detect antibodies CD11b+, F4 / 80+ and IL-1β respectively. The results are as follows...

Embodiment 2

[0029] Example 2 Effect of 14-3-3 Inhibitor BV02 on Sepsis Model Mice

[0030] 4-6 weeks old SPF grade female C57BL / 6 mice were injected with the same amount of BV02 and DMSO (both 10 mg / kg) into the tail vein respectively. After 12 hours, the mouse cecum ligation sepsis model was constructed, and the mice were observed and recorded. Rat survival, structured as figure 2 As shown in A.

[0031] 4-6 weeks old SPF grade female C57BL / 6 mice were injected with the same amount of BV02 and DMSO (both 10 mg / kg) into the tail vein, and after 12 hours, the mouse cecal ligation sepsis model was constructed, and the mouse lungs and Peritoneal lavage fluid. The lung tissue was ground, filtered, and performed specific flow cytometry antibody staining together with peritoneal lavage fluid to detect antibodies CD11b+, F4 / 80+, and ly6G respectively + and IL-1β, the results were as figure 2 B. figure 2 C and figure 2 D shows.

[0032] figure 2 A The results showed that the survival...

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Abstract

The invention belongs to the technical field of immunotherapy, and discloses a drug for treating sepsis, which is characterized in that the drug can inhibit 14-3-3 protein. According to the invention,14-3-3 molecules are used as targets to be applied to treatment of sepsis for the first time. Immunotherapy of sepsis can be achieved through the 14-3-3 targeting method. The method has the advantages of improving the survival rate of sepsis, relieving inflammation and the like, is suitable for comprehensive treatment of sepsis and is suitable for clinical application and popularization.

Description

technical field [0001] The present invention relates to the technical field of immunotherapy, and more specifically, relates to the application of intervention 14-3-3 in the treatment of sepsis. Background technique [0002] Sepsis refers to the systemic inflammatory response syndrome (SIRS) caused by infection. It is clinically confirmed that there are bacteria or highly suspicious infection foci, and it is the main cause of death in critically ill patients. According to its severity, it can be divided into sepsis, severe sepsis and septic shock. Its pathogenesis is mainly due to the pathological damage of the body caused by the "inflammatory storm" produced by immune cells. [0003] Studies have shown that the NLRP3 inflammasome promotes the maturation and secretion of IL-1β, which plays an important role in promoting the development of sepsis, but the specific mechanism of its activation is still unclear. Although various countries have devoted a lot of manpower, materi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P31/04G01N33/68
CPCA61K45/00A61P31/04G01N33/6869
Inventor 黄曦曹灿吴永坚
Owner THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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