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Application of pattern recognition receptor Dectin-1 inhibitor in immune protection and immune tolerance induction of receptor grafts

A dectin-1, pattern recognition receptor technology, applied in the field of medicine, can solve the problems affecting the long-term prognosis of transplant recipients, heavy economic burden on patients, high price of anti-rejection drugs, etc., to reduce economic burden, reduce dosage, and reduce side effects Effect

Active Publication Date: 2020-08-18
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the anti-rejection drug commonly used clinically is tacrolimus. Long-term use can cause many adverse reactions, such as neurotoxicity, induction of opportunistic infection, or tumorigenesis, etc., which will affect the long-term prognosis of transplant recipients.
, and the price of anti-rejection drugs is high, and the economic burden of long-term patients is heavy

Method used

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  • Application of pattern recognition receptor Dectin-1 inhibitor in immune protection and immune tolerance induction of receptor grafts
  • Application of pattern recognition receptor Dectin-1 inhibitor in immune protection and immune tolerance induction of receptor grafts
  • Application of pattern recognition receptor Dectin-1 inhibitor in immune protection and immune tolerance induction of receptor grafts

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1 Experimental method

[0042] 1. Experimental animal model

[0043] A single 200 mg / kg dose of C57BL / 6 mice at 6-8 weeks was used to establish a diabetic model by intraperitoneal injection of STZ, and the diabetic model mice were used as recipients of islet transplantation. 6-8 week old Balb / c mice were used as islet transplantation donors.

[0044] 2. Methods of islet transplantation:

[0045] (1) Fully anesthetize the donor mouse Balb / c mouse, perfuse 2-2.5ml of collagenase retrogradely through the common bile duct, and after digesting gradient centrifugation, select 250-300 islets under a microscope and put them in a 37°C incubator Incubate for 12-24 hours.

[0046](2) The recipient mouse is black C57BL / 6, fully anesthetized, the quarter rib area skin is prepared, the right side is lying, an empty insulin syringe or a cylinder of similar shape is placed on the waist, the kidney is fully exposed, the drape is sterilized, and the longitudinal vertical cu...

Embodiment 2

[0056] Example 2 Evaluating the Immunoprotective Effect of Laminarin on Islet Transplantation

[0057] The experiment was carried out according to the method of Example 1, and the daily blood glucose of the above six groups of mice after transplantation was recorded. Mouse blood glucose>300mg / kg (16.7mmol / L) for two consecutive times can be regarded as rejection. Record the survival time of islet transplantation and make survival curve ( figure 1 ).

[0058] from figure 1 It can be seen in:

[0059] The average survival time of mouse islets in laminarin group (29) days was longer than that in PBS group (11) days (n=5, p<0.05).

[0060] The average survival time of mouse islets in the low-dose tacrolimus group (35) days was longer than that in the PBS group (11) days (n=5, p<0.05).

[0061] The average survival time of mouse islets in the high-dose tacrolimus group (41) days was longer than that in the PBS group (11) days (n=5, p<0.05).

[0062] The average survival time ...

Embodiment 3

[0068] Example 3 Effect of laminarin on the number of T cell subsets Th1, Th2 and Treg

[0069] Test according to the method of embodiment 1.

[0070] The spleens of mice in each group were collected 7 days after islet transplantation, crushed with injection pistons, filtered through 70 μm nylon mesh, treated with erythrocyte lysate and collected T lymphocytes, treated with Golgi inhibitors and collected After intracellular and extracellular staining of T cells, it was tested on the machine to detect Th1 (CD3 + CD8 - IFN-γ + ), Th2 (CD3 + CD8 - IL4 + ) and Treg (CD4 + CD25 + FoxP3 + ) number (mean±SD, n=5). Analysis results such as figure 2 Shown:

[0071] The Th1 content of the laminarin group was lower than that of the PBS group (19.64±1.115VS 23.36±0.7301, P=0.0002)%, and the Th2 content of the laminarin group was higher than that of the PBS group (2.882±0.4755VS1.686±0.2798, P=0.0013 )%, the content of Treg in laminarin group was higher than that in PBS group ...

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Abstract

The invention discloses an application of a pattern recognition receptor Dectin-1 inhibitor in immune protection and immune tolerance induction of a receptor graft, including an application of laminarin in inhibition of rejection reaction of a mouse graft and induction of immune tolerance. According to the invention, laminarin is proposed for the first time to inhibit rejection reaction after organ transplantation, the survival time of a graft is obviously prolonged, immune tolerance is induced under the synergistic effect of tacrolimus, and the combination effect is better; meanwhile, laminarin is proposed to inhibit graft rejection and induce immune tolerance by inhibiting dectin-1. According to the invention, a dectin-1 inhibitor laminarin and a low dosage of tacrolimus are combined foruse for the first time; the tacrolimus immunopotentiator has the advantages that the tacrolimus immunopotentiator can induce immune tolerance, the use dosage of tacrolimus can be reduced, the side effect caused by single use of full-dose tacrolimus is reduced, the economic burden of a patient is reduced, the life quality of an organ transplantation patient is improved, the application prospect isgood, Meanwhile, a new target and a new way are provided for regulating and controlling receptor rejection to transplanted organs and inducing immune tolerance.

Description

technical field [0001] The invention belongs to the technical field of medicine. It relates to the immunoprotective effect of pattern recognition receptor Dectin-1 inhibitors on recipient grafts and its application in inducing immune tolerance, more specifically, relates to the role of laminarin in inhibiting rejection of transplant recipients and inducing immune tolerance and the application of laminarin combined with anti-rejection drugs in inhibiting rejection of transplant recipients and inducing immune tolerance. Background technique [0002] Organ transplantation is currently one of the most effective means of treating various end-stage diseases. my country is currently the second largest organ transplant country in the world. After ten years of hard work, my country's organ donation work has made great progress. The demand is increasing day by day, so the demand and development potential of organ transplantation in our country is huge. [0003] However, organ transpl...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/715A61K31/436A61P37/06A61K36/03
CPCA61K45/00A61K31/715A61K36/03A61K31/436A61P37/06A61K2300/00
Inventor 马毅任翱李仲秋章旭之饶佳伟邓荣海
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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