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Use of apolipoprotein A-I in preparing medicaments for inhibiting G+ bacteria infection induced sepsis and tissue inflammation damnification

An apolipoprotein, sepsis technology, applied in antibacterial drugs, drug combinations, peptide/protein components, etc., can solve the problem of not being able to remove the toxicity of LTA

Inactive Publication Date: 2008-08-06
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have confirmed that although antibiotic treatment can kill G + bacteria, but cannot detoxify LTA
At present, there is no drug that can directly combat the toxicity of LTA and inhibit the systemic inflammatory response and tissue inflammatory damage caused by sepsis.

Method used

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  • Use of apolipoprotein A-I in preparing medicaments for inhibiting G+ bacteria infection induced sepsis and tissue inflammation damnification
  • Use of apolipoprotein A-I in preparing medicaments for inhibiting G+ bacteria infection induced sepsis and tissue inflammation damnification

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Embodiment 1 prepares ApoA-I

[0013] Separate and purify human plasma ApoA-I from human plasma precipitation IV (waste after extracting blood products from blood product enterprises), with a purity of 98% (patent application number 200610029114.4).

[0014] Plasma precipitation IV extracts and purifies ApoA-I through the following steps:

[0015] ①pH 7.365% ethanol-10mM NaHCO 3 liquid extraction;

[0016] ② pH 5.5 isoelectric point precipitation, and dissolved in pH 8.6 Tri-HCl-Urea solution;

[0017] ③Chloroform: ethanol (1:1) degreasing;

[0018] ④Equal volume of ethanol precipitation, take the supernatant;

[0019] ⑤ Concentration, pasteurization after dialysis, sterilization and filtration;

[0020] ⑥ Freeze drying.

Embodiment 2

[0022] ApoA-I inhibits LTA-induced acute lung injury (ALI), sepsis and systemic inflammatory response experiments

[0023] Eighteen BALB / C male mice were randomly divided into three groups:

[0024] (1) LTA group: mice were injected intravenously with LTA (20 mg / kg) to induce sepsis;

[0025] (2) ApoA-I treatment group: intravenous injection of ApoA-I (50 mg / kg) after LTA administration;

[0026] (3) Control group: the mice were injected with normal saline.

[0027] Blood samples were taken 24 hours after administration of ApoA-I to determine the concentrations of plasma IL-1β and TNF-α. The right lung was removed, and histological microscopic examination was performed after HE staining; the left lung was removed, and the concentrations of IL-1β and TNF-α in alveolar bronchial lavage fluid were determined. The results showed that: compared with the lung tissue morphology of the normal control group (Figure 1C), the lung tissue of the LTA group showed acute lung injury, show...

Embodiment 3

[0037] ApoA-I inhibits LTA to activate macrophages to release inflammatory factors to kill L-929 cells Experiments Isolate mouse peritoneal macrophages by conventional methods.

[0038] Divided into four groups: (1) LTA treatment group; (2) LTA+0.25μgApoA-I group; (3) LTA+12.5μgApoA-I group; (4) LTA+25μgApoA-I group. After co-cultivation in each group, macrophages were isolated, and then added to L-929 cells. After co-cultivation, the death rate of L-929 cells in each group was measured by MTT method.

[0039] The results showed that ApoA-I inhibited the release of inflammatory factors from macrophages activated by LTA, and presented a dose-effect curve.

[0040] Table 3 shows the killing effect of ApoA-I on L-929 cells by inhibiting the release of inflammatory factors from macrophages activated by LTA.

[0041] table 3

[0042] Group (n=4)

[0043] ** P<0.01, compared with group (1).

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Abstract

The invention belongs to a pharmaceutical field, relates to a novel purpose of an apolipoprotein A-I (ApoA-I) in pharmacy, which carries out animal experiments and in vitro cell experiments with the apolipoprotein A-I (ApoA-I), the results of which prove that ApoA-I can directly combine and eliminate the toxicity of lipoteichoic acid(LTA), remarkably inhibits the LTA to induce and activate macrophage to release inflammatory factors, systemic inflammatory reaction and damages of organs and tissues (lung). The experiments in the invention prove that ApoA-I has special function of combining and neutralizing the LTA toxicity and can inhibit G <+> germ to infect sepsis and induce systemic inflammatory reaction and inflammatory damages of tissues and provides a novel treatment approach for sepsis and inflammatory damages of tissues induced by the G <+> germ, which has potential clinical application value.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a new application of apolipoprotein A-I (ApoA-I) in pharmacy, in particular to apolipoprotein A-I in the preparation of inhibitory G + Use in bacterial infection-induced sepsis and systemic inflammatory response. Background technique [0002] The study reported that LTA is G + A toxic component of the bacterial cell wall that acts as an immunostimulant triggering systemic inflammatory response syndrome in infectious sepsis [J.H.M. acid.Infect.Immun.71(2003)3280-3284.], activate macrophages and neutrophils, release inflammatory cytokines (TNF-α, IL, etc.), leading to tissue inflammatory damage, septic shock, multiple organ Dysfunction and failure (MODS, MOF) [S.Bhakdi, T.Klonisch, P.Nuber, W.Fischer, Stimulation of monokine production by lipoteichoic acids, Infect.Immun.59(1991) 4614-4620; S.J.De Kimpe, M. Kengatharan, C. Thiemermann, and J.R. Vane, Thecell wall components peptidoglycan a...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P31/04A61P29/00
Inventor 吴满平焦艳玲
Owner FUDAN UNIV
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