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Application of mir-29 and its inhibitors in the preparation of anti-organ transplantation rejection drugs

A technology of antagomir-29, 1. antagomir-29, which is applied in the application field of preparing anti-organ transplant rejection drugs

Active Publication Date: 2019-02-19
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are no reports on its relationship with solid organ transplant rejection, anti-virus, etc.

Method used

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  • Application of mir-29 and its inhibitors in the preparation of anti-organ transplantation rejection drugs
  • Application of mir-29 and its inhibitors in the preparation of anti-organ transplantation rejection drugs
  • Application of mir-29 and its inhibitors in the preparation of anti-organ transplantation rejection drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1: antagomiR-29 significantly inhibits acute rejection after organ transplantation

[0033] experimental method:

[0034] 1. Establishment of an allogeneic mouse neck heterotopic heart transplantation model

[0035] Heterotopic heart transplantation in the mouse neck was performed using the improved Cuff technique, that is, C57BL / 6 mice were selected as recipients, BALB / c mice were used as donors, and the ascending aorta of the donor heart was cuffed with the common carotid artery of the recipient mice. Cannula and cerclage fixation; donor cardiopulmonary artery and recipient mouse external jugular vein cannula and cerclage fixation. After the operation, the transplanted heart was deemed to have been rejected if there was no sign of beating by visual inspection and touch. If the beating stopped within 48 hours or the recipient mice died, it was considered as a failure of the model.

[0036] 2. Experimental grouping

[0037] The experiment was divided into tw...

Embodiment 2

[0048] Example 2: antagomiR-29 significantly inhibits antibody-mediated rejection (AMR)

[0049] Summarizing the previous experiments, we found that antagomiR-29 can effectively play an anti-graft rejection role and prolong the survival time of grafts. The possible mechanisms are as follows: 1. AntagomiR-29 may effectively inhibit the infiltration of immune cells in the transplanted heart by inducing immune cell apoptosis and inhibiting the proliferation of immune cells; 2. AntagomiR-29 may participate in antibody-mediated immunity by regulating B cells. immune rejection (AMR, antibody mediated rejection). Since chronic rejection has become the most important cause of long-term graft failure, we first focus on B cells. First, we adoptively reinfuse sensitized B cells into BALB / c--C57BL / 6-Rag2 - / - Mice were transplanted with hearts, and the survival of the grafts was observed.

[0050] experimental method:

[0051] 1. Establishment of an allogeneic mouse neck heterotopic he...

Embodiment 3

[0063] Example 3: Endogenous inhibition of miR-29 expression by sponge technology can significantly affect the development of B cells, reducing the number and proportion of peripheral B cells

[0064] experimental method:

[0065] 1. Acquisition of miR-29Sponge (GS29) transgenic mice

[0066] The miR-29Sponge (GS29) transgenic mice were constructed by Southern Model Organisms Company. The obtained heterozygous mice were crossed with C57BL / 6 mice for more than 10 generations. Total RNA was extracted from the mouse tail, reversed, and the level of miR-29 was quantitatively detected. A CT value lower than 20 was regarded as a transgenic mouse.

[0067] Upstream primer: 5'-GAGCAAAGACCCCAACGAGAAG-3', SEQ ID NO.4

[0068] Downstream primer: 5'-TCTACA A ATGTGGTATGGCTGAT-3', SEQ ID NO.5.

[0069] 2. Flow cytometric detection of B cell subsets

[0070] GS29 mice were taken, and wild mice of the same littermate were used as controls. After the mice were sacrificed, the skin of the...

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Abstract

The invention relates to the technical field of biomedicine, in particular to mir-29 and application of an inhibitor thereof in preparing medicine resisting organ transplant rejection, and provides new medical application of miR-29. The new medical application includes that the inhibitor of miR-29 can remarkably inhibit T cell mediated acute rejection after allogeneic organ transplant; the inhibitor of miR-29 can remarkably influence B cell development, induce B cell apoptosis and reduce number and proportion of peripheral B cells so as to effectively inhibit antibody mediated immunological rejection after allogeneic organ transplant. The invention provides a new prevention and treatment means for treating rejection, especially antibody mediated acute-chronic rejection after allogeneic organ transplant.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the new medical application of miR-29, specifically including the application of miR-29 and its inhibitors in the preparation of anti-organ transplantation rejection drugs. Background technique [0002] Organ transplantation is the most effective clinical method for treating terminal diseases. With the clinical application of new immunosuppressants such as CsA and FK, the occurrence of acute rejection has been effectively reduced, the survival period of organ transplants has been significantly prolonged, and the lives of many patients with end-stage organs have been saved. However, the rejection after organ transplantation is still the main obstacle affecting the long-term survival of the graft, especially the chronic rejection with the pathological manifestations of graft fibrosis and vascular intimal hyperplasia has become the most important cause of long-term graft failure...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P37/06
CPCA61K45/00
Inventor 王全兴丁国善刘芳郭猛张铭健展洋洋
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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