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Application of SLAMF7 recombinant protein in preparation of drugs for treating sepsis

A technology for sepsis and drugs, which is applied in the field of preparation of drugs for the treatment of sepsis, and can solve the problems of lack of inflammatory storm and high mortality

Active Publication Date: 2021-03-23
THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although various countries have devoted a lot of manpower, material and financial resources to the treatment of sepsis, its mortality rate is still high. One of the main reasons is the lack of early effective drugs to suppress the generation of inflammatory storms.

Method used

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  • Application of SLAMF7 recombinant protein in preparation of drugs for treating sepsis
  • Application of SLAMF7 recombinant protein in preparation of drugs for treating sepsis
  • Application of SLAMF7 recombinant protein in preparation of drugs for treating sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 The expression of SLAMF7 in patients with sepsis and its clinical correlation

[0023] 5ml of peripheral blood was collected from 81 healthy volunteers and 83 patients with sepsis. Lymphocyte separation medium was used to separate PBMC, and the expression of SLAMF7 in CD11b+ macrophages was detected by flow cytometry. In addition, 30 cases of sepsis patients were selected, and different treatment periods were detected, including before treatment (Pre-treatment), after 1 day of treatment (post-1day), after 3 days (post-3day), after 5 days (post-5day), The ratio of SLAMF7+CD11b+ cells after 7 days (post-1day).

[0024] figure 1 A The results showed that the expression of SLAMF7 in CD11b+ cells was significantly upregulated in sepsis patients compared with healthy people.

[0025] figure 1 The results of B showed that the proportion of SLAMF7+CD11b+ cells was positively correlated with the level of inflammatory index CRP (r=0.56), indicating that the expressio...

Embodiment 2

[0028] Example 2 Effect of SLAMF7 recombinant protein on sepsis model mice

[0029] Using 4-6 weeks of SPF grade female C57BL / 6 mice, construct a mouse cecal ligation sepsis model (CLP) (construct a cecal ligation sepsis model mouse according to conventional methods in the field), and inject intraperitoneally after 2 hours, etc. Amount of SLAMF7 recombinant protein (rmSLAMF7) and 0.9% Nacl (Control), after 12 hours, observe and record the survival rate of mice, the results are as follows figure 2 As shown in A.

[0030] Using 4-6 weeks of SPF grade female C57BL / 6 mice, a mouse model of cecal ligation sepsis was established. Two hours later, the same amount of SLAMF7 recombinant protein (rmSLAMF7) and 0.9% Nacl (Control) were injected intraperitoneally. After 12 hours, the lung lobules were fixed with 4% paraformaldehyde, and the lung tissue sections were stained with H&E and observed under a microscope. The results were as follows: figure 2 Shown in B.

[0031] The remai...

Embodiment 3

[0038] Example 3 Effect of SLAMF7 gene deficiency on sepsis model mice.

[0039] Using 4-6 weeks of SPF grade female C57BL / 6 mice, a wild-type (WT) mouse and SLAMF7 gene-deficient (SLAMF7 KO) cecal ligation sepsis model (CLP) model was constructed. Observe and record the mouse survival rate, the results are as follows: image 3 As shown in A.

[0040]4-6 weeks old SPF grade female C57BL / 6 mice were used to construct a mouse cecal ligation sepsis model. After 12 hours, the lung lobules were fixed with 4% paraformaldehyde, and the lung tissue sections were stained with H&E and observed under a microscope. The results Such as image 3 Shown in B.

[0041] Grind the remaining lung tissue to keep the supernatant (Lung), and also grind the liver to keep the supernatant (Liver) and collect the supernatant of peritoneal lavage fluid (PL) for ELISA, and detect TNF-α, IL1-β, IL in the supernatant respectively The expression level of -6, the result as image 3 C shown.

[0042] The...

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Abstract

The invention belongs to the technical field of cell therapy, and discloses application of SLAMF7 recombinant protein in preparation of drugs for treating sepsis. According to the invention, the SLAMF7 is used as a target for diagnosis / immunotherapy of the sepsis for the first time. The sepsis can be diagnosed by detecting the expression of the SLAMF7 in macrophages. The immunotherapy of the sepsis can be realized by utilizing the SLAMF7 recombinant protein and an immunotherapy method thereof; and the method has the advantages of improving the survival rate, slowing down inflammatory factor storm, relieving lung pathological injury and the like, and is suitable for comprehensive treatment of the sepsis.

Description

technical field [0001] The invention relates to the technical field of cell therapy, and more specifically, relates to the application of SLAMF7 recombinant protein in the preparation of drugs for treating 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 incomplete data released by the Global Sepsis Alliance, the number of deaths due to sepsis exceeds the sum of deaths from prostate cancer, breast cancer and AIDS. There are about 18 million severe sepsis cases worldwide every year. The pathogenesis of sepsis is mainly due to the pathological damage of the body caused by the "inflammatory storm" produced by immune cells. Although various countries have devoted a lot of manpower, material and financial resources to the treatment of sepsis,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883A61K38/17A61K45/00A61P31/00A61P11/00
CPCC12Q1/6883A61K38/1774A61K45/00A61P31/00A61P11/00C12Q2600/158
Inventor 黄曦劳娟凤李淼明思奇
Owner THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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