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Application of targeted complement inhibitors in the preparation of drugs for improving brain-dead donor livers

A complement inhibitor and brain death technology, applied in the field of biomedicine, to reduce mitochondrial damage in liver and liver cells, improve oxidative stress damage, and have strong targeting effects

Active Publication Date: 2019-09-06
THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, based on the background of BDD liver transplantation, there are few reports on the mechanism of complement in injury (BDI, IRI, cascade injury) and repair

Method used

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  • Application of targeted complement inhibitors in the preparation of drugs for improving brain-dead donor livers
  • Application of targeted complement inhibitors in the preparation of drugs for improving brain-dead donor livers
  • Application of targeted complement inhibitors in the preparation of drugs for improving brain-dead donor livers

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0028] Preparation of targeting complement inhibitor CR2-Crry: prepared by linking complement receptor 2 (CR2) to membrane binding regulatory factor (Crry). For specific preparation, please refer to: Atkinson C, Song H, Lu B , etal. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection. J ClinInvest. 2005; 115(9): 2444-2453 Preparation of CR2-Crry fusion protein in Methods. The prepared amino acid sequence of the targeted complement inhibitor CR2-Crry used in the examples is shown in SEQ ID NO.1, which contains 585 amino acids.

[0029] Complement C3 knockout mice (C3 - / - mice, C3 knockout mice) are B6; 129S4-C3 tm1Crr / J strain, purchased from The Jackson Laboratories (Bar Harbor, Maine, USA).

Embodiment 1

[0031] 1. Establishment of the overall model related to the experiment

[0032] After the mice were anesthetized, the arterial pressure of the mice was monitored through carotid artery intubation, and the mice were fixed on the surgical rack in a supine position, and a tracheotomy was performed to connect the catheter. Then the mouse was changed to the prone position, and a 1mm hole was drilled about 0.2cm lateral to the sagittal line of the mouse skull, and a 4F Fogarty catheter was inserted into the brain, with the tip pointing to the brainstem. Inject normal saline into the catheter balloon at a rate of 4 μl per minute, gradually inflate the balloon, and increase intracranial pressure until spontaneous breathing stops (the total amount of normal saline is 80 μl±25 μl). The diagnosis of brain death was confirmed by recording the presence or absence of corneal reflexes and respiratory arrest tests, and monitoring arterial pressure fluctuations. After operation, the mice were...

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Abstract

The invention discloses an application of a targeted complement inhibitor in preparation of drugs for improving brain death donor livers. The application of the targeted complement inhibitor in preparation of the drugs for improving the brain death donor livers is characterized in that a complement receptor 2 (CR2) is utilized to connect a membrane binding regulatory factor Crry; with targeted binding of the CR2 to complement activation and local injury, the membrane-binding regulatory factor utilized to regulate different stages of complement cascade, and a mouse brain death model established, the changes of the liver functions between a CR2-Cryy treatment group and a control group are compared; results indicate that the targeted complement inhibitor CR2-Crry is effective in improving donor liver injury after brain death and can reduce liver inflammatory response, oxidative stress damage and hepatocyte apoptosis. The role of this complement inhibitor in improving donor liver functionafter brain death is further confirmed by complement knockout mice.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of a targeted complement inhibitor in the preparation of drugs for improving brain-dead liver donors. Background technique [0002] Liver transplantation has become the most effective method for the treatment of end-stage liver disease. However, the supply and demand ratio of organs is tight, and the donated liver cannot meet the needs of patients. Currently, the donated livers mainly come from brain-dead donors. Clinical studies have shown that: compared with living donor liver transplantation, the quality of the donor liver after brain death is significantly reduced, and the incidence of early allograft dysfunction (early allograft dysfunction) or even primary non-function (primary no function, PNF) after transplantation is significantly higher. Mainly attributed to brain death-induced injury (Brain death-induced injury, BDI). Therefore, the rati...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61P1/16
Inventor 何松青林承杰雷彪胡志高袁观斗
Owner THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV
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