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Application of agmatine in preparing medicament for treating post-traumatic immunocom promise

An immune function, agmatine technology, applied in the field of medicine, can solve the problems of exacerbation of the latter, exacerbation, reduction of antigen-presenting cell clearance ability, etc.

Active Publication Date: 2014-10-08
THE THIRD AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIV OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, its dysfunction is manifested in the excessive activation of inflammatory cells and the release of a large number of inflammatory mediators, on the other hand, the reduced ability of antigen-presenting cells to clear pathogenic microorganisms and apoptotic / necrotic cells, and at the same time, the anti-infective immune function mediated by T cells is affected. inhibition
Current clinical treatment measures either take into account the former but aggravate the latter (such as traditional steroids, non-steroidal anti-inflammatory drugs) or take the latter into account but aggravate the former (such as interferon gamma), although immune enhancers can be used Combined strategy with anti-inflammatory drugs (such as thymosin + ulinastatin), but its efficacy needs to be improved urgently

Method used

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  • Application of agmatine in preparing medicament for treating post-traumatic immunocom promise
  • Application of agmatine in preparing medicament for treating post-traumatic immunocom promise
  • Application of agmatine in preparing medicament for treating post-traumatic immunocom promise

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Corrective effect of agmatine on hypofunction of splenocytes in traumatized mice

[0029] C57BL / 6 mice were subjected to double hindlimb femur fracture combined with 40% orbital bleeding to construct a severe traumatic blood loss model. Compared with the control group, the immune function of the mice after severe trauma was suppressed, and the proliferation ability of splenocytes was significantly reduced, and the secretion of interferon-γ (IFN-γ) and interleukin-2 (IL-2) was significantly reduced.

[0030] Agmatine was administered retroperitoneally to severely traumatized mice, and 100mg / kg, 200mg / kg, and 400mg / kg agmatine were given immediately after injury (once a day, the treatment time was 1 day). After treatment, the severe injury was significantly improved. Trauma-induced immunosuppression, manifested in a dose-dependent increase in the ability of splenocytes to proliferate and secrete IFN-γ and IL-2 (see figure 1 ,2).

Embodiment 2

[0031] Example 2 Effect of agmatine on secretion function of splenic macrophages and peritoneal macrophages in traumatized mice

[0032] The model preparation and agmatine treatment of traumatized mice were the same as in Example 1.

[0033] Compared with the control group, the secretion of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the spleen macrophages and peritoneal macrophages of severely traumatized mice stimulated by endotoxin (LPS) in vitro was significantly reduced , treated with agmatine (100mg / kg, 200mg / kg and 400mg / kg) (once a day for 1 day), after treatment, can significantly up-regulate the secretion of splenic macrophages and peritoneal macrophages in traumatized mice function (see Figure 3, 4).

Embodiment 3

[0034] Example 3 Effect of Agmatine on Mortality of Traumatized Mice After LPS Challenge

[0035] The trauma mouse model is the same as in Example 1. Agmatine (100mg / kg, 200mg / kg and 400mg / kg immediately after injury) was administered retroperitoneally to severely traumatized mice (once a day, the treatment time was 1 day), and LPS challenge was performed 24 hours after injury (LPS 25mg / kg, retroperitoneal injection), and additional agmatine (400mg / kg, retroperitoneal injection) treatment (once a day, the treatment time is 1 day). The results showed that compared with the simple LPS challenge group, severe trauma could significantly increase the mortality of LPS challenge model mice (trauma + LPS vs LPS, 80% vs 20%), and agmatine intervention treatment (100mg / kg , 200mg / kg and 400mg / kg) can dose-dependently reduce the mortality of LPS-challenged mice (40%, 33.33%, 25%, see Figure 5 ).

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Abstract

The invention relates to application of agmatine in preparing a medicament for treating post-traumatic immunocom promise. Experiments on a mouse are carried out by adopting an intraperitoneal administration manner, and observation in a traumatic model proves that the agmatine has an effect of treating post-traumatic immunocom promise.

Description

field of invention [0001] The invention relates to the field of medicine, in particular to the use of agmatine in the preparation of medicines for treating post-traumatic hypoimmunity. Background technique [0002] It is well known that in the pathological process of severe trauma, systemic inflammatory response syndrome (SIRS), sepsis, and multiple organ dysfunction syndrome (MODS), the body's immune system Dysfunction plays a big role. On the one hand, its dysfunction is manifested in the excessive activation of inflammatory cells and the release of a large number of inflammatory mediators, on the other hand, the reduced ability of antigen-presenting cells to clear pathogenic microorganisms and apoptotic / necrotic cells, and at the same time, the anti-infective immune function mediated by T cells is affected. inhibition. Current clinical treatment measures either take into account the former but aggravate the latter (such as traditional steroids, non-steroidal anti-inflam...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/155A61P37/04A61P29/00
Inventor 梁华平刘政
Owner THE THIRD AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIV OF PLA
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