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Human sDR5-Fc recombinant fusion protein and novel application thereof

A fusion protein, sdr5-fc technology, used in drug combinations, peptide/protein components, hybrid peptides, etc., to improve the survival rate, reduce the apoptosis rate of hepatocytes, and reduce liver pathological damage.

Active Publication Date: 2016-06-22
SHENZHEN ZHONGKE AMSHENN MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

) At present, whether sDR5 has a therapeutic effect on drug-induced liver injury, there is no report at home and abroad

Method used

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  • Human sDR5-Fc recombinant fusion protein and novel application thereof
  • Human sDR5-Fc recombinant fusion protein and novel application thereof
  • Human sDR5-Fc recombinant fusion protein and novel application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1: Human sDR5-Fc recombinant fusion protein can block TRAIL-induced liver cell apoptosis

[0058] The HepG2 cells in the logarithmic growth phase were plated on a 96-well plate, and the same concentration of actinomycin D was added to each well to inhibit cell division, and 2-fold diluted TRAIL protein was added to each well to induce cell apoptosis. %CO 2 After incubating in the incubator for 18-22 hours, add freshly prepared 20:1 mixed MTS / PMS chromogenic solution 20ul / well, continue culturing in the incubator for 3-4 hours, and detect its A490-A630 with a microplate reader value. Thus, the EC90 value of TRAIL killing activity was calculated.

[0059] HepG2 cells in the logarithmic growth phase were plated on a 96-well plate, the same concentration of actinomycin D was added to each well to inhibit cell division, and the same concentration of TRAIL protein was added to each well to induce 90% cell apoptosis. 2-fold diluted human sDR5-Fc recombinant fusion p...

Embodiment 2

[0061] Example 2: Human sDR5-Fc antibody fusion protein in the treatment of APAP-induced liver injury

[0062] (1) 40 C57BL / 6 male mice were equally divided into 4 groups (normal saline group, 0.1mg / kg sDR5-Fc group, 1mg / kg sDR5-Fc group, 10mg / kg sDR5-Fc group, the sequence of sDR5-Fc is SEQ ID NO .1), 10 mice in each group, each mouse was given 400mg / kgAPAP by intragastric administration, and after 1 hour, each group of mice was given physiological saline, 0.1mg / kgsDR5-Fc, 1mg / kgsDR5-Fc, 10mg / kg sDR5-Fc, the administration volume was 10ml / kg, blood was collected from the submandibular vein of each mouse at 6h, 24h, 32h and 48h after APAP administration, the serum was separated, and the serum transaminase level was detected. The mice were sacrificed at 48 hours, part of the liver was fixed in 4% PFA, embedded in paraffin, sectioned, HE stained, TUNEL stained, and TRAIL immunohistochemical stained.

[0063] The results are displayed (see figure 2 ): 10mg / kgsDR5-Fc recombinan...

Embodiment 3

[0066] Example 3: Synergistic treatment of APAP-induced liver injury by human sDR5-Fc recombinant fusion protein and NAC

[0067] Forty C57BL / 6 male mice were equally divided into 4 groups (normal saline group, 10mg / kg sDR5-Fc group, 100mg / kgNAC group, 10mg / kg sDR5-Fc and 100mg / kgNAC combined administration group, the sequence of sDR5-Fc is SEQ ID NO.1), 10 mice in each group, each mouse was given 500mg / kgAPAP by intragastric administration, and after 1 hour, each group of mice was given physiological saline, 10mg / kgsDR5-Fc, 100mg / kgNAC, 10mg / kg NAC by intraperitoneal injection, respectively. kgsDR5-Fc and 100mg / kgNAC were administered in combination, and the administration volume was 10ml / kg. 24 hours after APAP administration, blood was collected from the submandibular vein of each mouse, the serum was separated, and the level of serum transaminases was detected.

[0068] The results are displayed (see image 3 ): 10 mg / kg sDR5-Fc recombinant fusion protein and 100 mg / kg NA...

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Abstract

The invention relates to human sDR5-Fc recombinant fusion protein and application of the human sDR5-Fc recombinant fusion protein to preparation of medicine for preventing and treating drug induced liver injury. Through long-time study of the inventor, the protein gene sequence is selected again, and the novel human sDR5-Fc recombinant fusion protein provided by the invention is obtained. Through a great number of experiments, the human sDR5-Fc recombinant fusion protein can obviously reduce the serum transaminase level in various mouse drug induced liver injury models; the liver pathologic damage is reduced; the liver cell apoptosis rate is obviously reduced; the mouse survival ratio is improved. The human sDR5-Fc recombinant fusion protein is used as novel candidate medicine for preventing and treating the drug induced liver injury; the treatment range is wide; targets are specific; the action is special and fast; the curative effect is obvious; the safety is high; great development potential is realized.

Description

technical field [0001] The invention relates to the field of recombinant protein and medicine, in particular to a human sDR5-Fc recombinant fusion protein and its application in the preparation of drugs for preventing and treating drug-induced liver injury. Background technique [0002] Drug-induced liver injury (DILI) refers to liver injury induced by various prescription or over-the-counter chemical drugs, biological agents, traditional Chinese medicines, natural medicines, health products, dietary supplements and their metabolites, and even excipients. liver damage. Drug-induced liver injury may occur in patients with or without underlying liver diseases in the past after taking drugs. DILI is one of the most common and serious adverse drug reactions, and severe cases can cause acute liver failure (ALF) or even death. Drug-induced liver injury is the most common reason new drugs are discontinued and withdrawn from the market. In my country, due to the continuous increa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K38/19A61P1/16
Inventor 万晓春陈倩张青梅
Owner SHENZHEN ZHONGKE AMSHENN MEDICINE CO LTD
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