Application of DOR agonist in preparation of medicine for resisting renal fibrosis

A kidney fibrosis and agonist technology, applied in the field of medicine, can solve the problems of expensive medical expenses, high morbidity and poor prognosis, and achieve the effect of reducing fibrotic lesions

Active Publication Date: 2021-08-06
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chronic kidney disease has become another major disease that seriously threatens human health after cardiovascular and cerebrovascular diseases, tumors, and diabetes. It has a high incidence rate and poor prognosis, and will eventually develop into end-stage renal failure. patient quality of li

Method used

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  • Application of DOR agonist in preparation of medicine for resisting renal fibrosis
  • Application of DOR agonist in preparation of medicine for resisting renal fibrosis
  • Application of DOR agonist in preparation of medicine for resisting renal fibrosis

Examples

Experimental program
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Effect test

Embodiment 1

[0062] This example studies the effects of TGF-β1 and DOR activation on NRK-52E cells. Specific experimental results such as figure 1 Shown in the figure (A): DOR expression in NRK-52E cells. Western blotting was used to detect the expression of DOR in these cells (24-72h). (B): mRNA level of DOR in NRK-52E cells. (C): Effect of TGF-β1, UFP-512 and Naltrindole on cell viability. 10ng / ml of specific DOR agonist UFP-512 at different concentrations (0, 1, 5, 10 μM) was added to the culture medium for 24-48h, and the cell viability was measured with a cell counting kit (CCK 8). Among them, C: control group. T: 10 ng / ml TGF-β1. U: UFP-512. N: Naltrindole (inhibitor of DOR). T+U1: 10 ng / ml TGF-β1 + 1 μM UFP-512. T+U5: 10 ng / ml TGF-β1 + 5 μM UFP-512. T+U10: 10 ng / ml TGF-β1 + 10 μM UFP-512. N1: 1 μM Naltrindole. N5: 5 μM Naltrindole. N5+U1: 5 μM Naltrindole + 1 μM UFP-512. N5+U5: 5 μM Naltrindole + 5 μM UFP-512. N5+U10: 5 μM Naltrindole + 10 μM UFP-512.

[0063] figure...

Embodiment 2

[0066] This example studies the effect of DOR activation on TGF-β1-induced morphological changes. The result is as figure 2 As shown in the figure: (A): The effect of TGF-β1 and UFP-512 on cell morphology changes under light microscope. NRK-52E cells were incubated with 10ng / ml TGF-β1 for 24-48h, different concentrations (0, 1, 5, 10μM) of UFP-512, and the cell morphology was observed under a light microscope. (B): Immunofluorescent staining of NRK-52E cells. The cells were treated with drugs for 24 hours, and the cell morphology was observed by β-tubulin immunofluorescent staining. Among them, C: control group. T: TGF-β1. U: UFP-512. N: Naltrindole. T+U1: 10 ng / ml TGF-β1 + 1 μM UFP-512. T+U5: 10 ng / ml TGF-β1 + 5 μM UFP-512. T+U10: 10 ng / ml TGF-β1 + 10 μM UFP-512. N5+U1: 5 μM Naltrindole + 1 μM UFP-512. N5+U5: 5 μM Naltrindole + 5 μM UFP-512. N5+U10: 5 μM Naltrindole + 10 μM UFP-512.

[0067] The results showed that the NRK-52E cells in the control group (untreate...

Embodiment 3

[0069] This example studies the effect of DOR activation on cell migration induced by TGF-β1. The result is as image 3 Shown, (A): Effects of TGF-β1 and UFP-512 on cell migration. (B): Effect of DOR activation or inactivation on cell migration. (C): Effect of Naltrindole and UFP-512 on cell migration. The NRK-52E cell layer on the culture dish was scraped off with a micropipette and observed under a microscope before and after 24 hours of drug treatment. Among them, C: control group. T: TGF-β1. U: UFP-512. N: Naltrindole. T+U1: 10 ng / ml TGF-β1 + 1 μM UFP-512. T+U5: 10 ng / ml TGF-β1 + 5 μM UFP-512. T+U10: 10 ng / ml TGF-β1 + 10 μM UFP-512. N5+U1: 5 μM Naltrindole + 1 μM UFP-512. N5+U5: 5 μM Naltrindole + 5 μM UFP-512. N5+U10: 5 μM Naltrindole + 10 μM UFP-512.

[0070] The results showed that TGF-β1 treatment increased cell migration, while UFP-512 reversed the effect of TGF-β1. On the other hand, UFP-512 or / and Naltrindole had no significant effect on cell migration ...

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Abstract

The invention belongs to the technical field of medicines, and mainly relates to application of a DOR agonist in preparation of a medicine for resisting renal fibrosis. The application of the DOR agonist is as follows: a1, a2, a3 or a4, a1, preparing a medicine for preventing and/or treating renal fibrosis; a2, prevention and/or treatment of renal fibrosis; a3, activating and/or inhibiting DOR-related cell and molecular signal pathways; and a4, establishing an in-vitro model for activating the DOR so as to prevent and/or treat renal fibrosis. It is found for the first time that by adopting a specific DOR agonist (such as UFP-512) to activate DOR, signal channels such as Smad, p38, Akt and the like can be adjusted, and the specific DOR agonist can act on a transcription factor Snail to regulate and control renal tubulointerstitial transformation (EMT), so that the process of renal fibrosis is relieved. The invention expounds the relationship between the DOR and the renal fibrosis for the first time, reveals that the DOR on the kidney cells is activated to effectively relieve the fibrosis lesion of the kidney cells, provides a new way for preventing and treating the pathological change of the renal fibrosis, and has important scientific value and clinical significance.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of a DOR agonist in the preparation of medicines for resisting renal fibrosis. Background technique [0002] Renal fibrosis is a common feature of all chronic kidney diseases (CKD), and it is also a common pathological process that progresses to end stage renal disease (ESRD). Chronic kidney disease refers to the general term for a group of kidney diseases that have damaged the structure or function of the kidneys for more than 3 months, with or without decreased glomerular filtration rate, including chronic glomerulonephritis / nephrotic syndrome, diabetic nephropathy and hereditary Kidney disease (such as polycystic kidney disease, Alport syndrome) and other kidney diseases. During the progression of renal fibrosis, normal tissue is replaced by fibrotic tissue, renal function declines progressively, and eventually chronic renal failure (CRF) occurs, ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/4725A61P13/12
CPCA61K45/00A61K31/4725A61P13/12Y02A50/30
Inventor 夏萤何小舟罗凤宝
Owner FUDAN UNIV
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