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Therapeutic effect of ghrelin and L-serine compound on sepsis

A technology of therapeutic action and ghrelin, which is applied to medical preparations containing active ingredients, pharmaceutical formulations, peptide/protein components, etc., can solve the problems of incomplete elucidation of the pathogenesis, failure to achieve good results, and multiple organ function damage. , to relieve sepsis anemia, improve blood coagulation time, and improve the effect of inflammatory response

Pending Publication Date: 2020-08-11
AFFILIATED HOSPITAL OF NANTONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] The present invention provides the therapeutic effect of ghrelin combined with L-serine compound on sepsis, which solves the problem in the prior art that the pathogenesis of sepsis has not been fully elucidated, and the pathological mechanism of sepsis often involves multiple systems in the whole body. Cause multiple organ dysfunction, a single treatment method can not achieve good results and other technical problems

Method used

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  • Therapeutic effect of ghrelin and L-serine compound on sepsis
  • Therapeutic effect of ghrelin and L-serine compound on sepsis
  • Therapeutic effect of ghrelin and L-serine compound on sepsis

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Experimental program
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Effect test

Embodiment 1

[0033] The therapeutic effect of ghrelin on sepsis, the steps are:

[0034] In the first step, basic research is carried out at both in vivo and in vitro levels. The in vivo animal model experiment uses the mouse sepsis model CLP with cecal ligation and puncture;

[0035] In the second step, primary cells corresponding to the small intestine, liver and spleen were used in the in vitro experiment, specifically small intestinal epithelial cells, liver parenchymal cells and peritoneal macrophages. Under the condition of exogenous ghrelin, the expression changes of iron metabolism-related proteins in each tissue / cell, the expression of iron metabolism-related proteins and the changes of cellular iron content after activation or blocking of GHSR1a receptor and MAPK (ErK1 / 2) signaling pathway, and Monitor the changes of serum iron content, erythropoiesis and tissue iron content in mice.

[0036] It is verified that Ghrelin / GHSR1a / MAPK participates in the regulation of iron mobiliza...

Embodiment 2

[0040] The therapeutic effect of L-serine combined with ghrelin on sepsis, the steps are:

[0041] In the first step, the model used is a mouse demyelination model. The white matter damage was caused by stereotaxic injection of lysolecithin LPC into C57 / BL6 mice, and then treated with L-serine. The specific steps were as follows: intraperitoneal injection of chloral hydrate Mice were anesthetized and fixed on a brain stereotaxic apparatus;

[0042] The second step is to sterilize and incise the mouse scalp to expose the bregma and read the coordinates of the bregma;

[0043] The third step is to determine the position of the corpus callosum, open a bone window at the corresponding skull, move the vertical scale of the stereotaxic instrument, place the needle of the micro-sampler at the bone hole, and determine the coordinates of the corpus callosum with reference to the stereotaxic map of the mouse brain. The injection volume is 1.5 μL, the injection speed is 0.3 μL / min, the ...

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Abstract

The invention discloses therapeutic effect of a ghrelin and L-serine compound on sepsis. Experiments are carried out from an in-vivo level and an in-vitro level. An in-vivo animal model experiment adopts a cecum ligation puncture mouse sepsis model CLP. An in-vitro experiment adopts primary cells corresponding to the small intestine, the liver and the spleen of a mouse. The expression change of iron metabolism related protein in each tissue / cell of a false operation group, a cecum ligation puncture group and a condition of cecum ligation puncture with exogenous ghrelin is observed, the expression of the iron metabolism related protein and the change of cell iron content are observed after the a GHSR1a receptor and MAPK (ErK1 / 2) signal paths are activated or blocked, changes of serum iron content, erythrocyte generation and tissue iron content of the mouse are monitored, and it is verified that the ghrelin / GHSR1a / MAPK participates in regulation and control of iron mobilization among tissues of a body under a cecum ligation perforation model, increases serum iron, reduces hepcidin, promotes hemoglobin synthesis, and finally relieves sepsis anemia and tissue hypoxia injury.

Description

technical field [0001] The invention relates to the application technical field of ghrelin and L-serine compound, in particular to the therapeutic effect of ghrelin combined with L-serine compound on sepsis. Background technique [0002] Sepsis refers to life-threatening organ dysfunction caused by the body's dysregulated response to infection (Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3)[J]. JAMA, 2016, 315(8):801-810.). Sepsis can be caused by a variety of etiologies, mainly manifested as the continuous high concentration of inflammatory mediators in the blood, and severe cases can lead to multiple organ failure and life-threatening. [0003] Sepsis-associated encephalopathy (SAE) is a brain dysfunction caused by sepsis. (Zhang LN, Wang XT, Ai YH, et al.Epidemiological features and riskfactors of sepsis-associated encephalopathy in intensive care unit patients:2008-2011[J].Chin Med J(Engl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/22A61K31/198A61P31/04
CPCA61K38/2214A61K31/198A61P31/04A61K2300/00
Inventor 袁晓宇顾袁瑢李华镭姜岱山潘闽骆倩倩
Owner AFFILIATED HOSPITAL OF NANTONG UNIV
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