Application of sglt2 inhibitor in the preparation of reagents for inhibiting glucose absorption by pmcs or peritoneal fibrosis

A glucose and inhibitor technology, applied in medical preparations containing active ingredients, pharmaceutical formulas, drug combinations, etc., can solve problems such as hypertrophy, mesothelial damage, and failure

Active Publication Date: 2021-02-26
THE FIRST AFFILIATED HOSPITAL OF WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, high glucose can significantly damage PMCs, causing them to hypertrophy, senescence, and apoptosis, thereby damaging the mesothelial layer, reducing the peritoneal defense ability against infection and fibrosis, and finally leading to peritoneal fibrosis and ultrafiltration failure

Method used

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  • Application of sglt2 inhibitor in the preparation of reagents for inhibiting glucose absorption by pmcs or peritoneal fibrosis
  • Application of sglt2 inhibitor in the preparation of reagents for inhibiting glucose absorption by pmcs or peritoneal fibrosis
  • Application of sglt2 inhibitor in the preparation of reagents for inhibiting glucose absorption by pmcs or peritoneal fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] This embodiment provides a method for isolating and culturing PMCs from human peritoneal dialysate and detecting the expression of SGLT2 in the PMCs and human peritoneal tissue.

[0041] 1. Isolation, culture and passage of PMCs

[0042] Separation: Aseptically collect the peritoneal fluid samples of ESRD patients left at night within 2 weeks after PD catheterization; divide the PDS into 250ml centrifuge tubes on a sterile cell operating table, centrifuge at 400g at 4°C for 10 minutes; discard Supernatant, resuspend the pelleted cells in PBS, transfer to a 15ml sterile centrifuge tube, centrifuge at 4°C and 400g for 5 minutes, and repeat: Discard the supernatant, resuspend the pelleted cells in PBS, transfer to Centrifuge a 15ml sterile centrifuge tube at 4°C and 400g for 5 minutes; discard the supernatant and replace with an appropriate amount of complete medium (DMEM / F12 medium) to resuspend the cells.

[0043] Culture: transfer the cell suspension to a 75ml cultur...

Embodiment 2

[0052] This example investigates the effect of SGLT2 inhibitors on the peritoneal absorption of glucose in rats, specifically:

[0053] 1. Effects of different doses of empagliflozin on blood glucose and peritoneal function in rats

[0054] Male SD rats at the age of 10-12 weeks with SPF grade were randomly divided into 4 groups (6 rats in each group): control group (gastric administration of water for injection), 1mg / kg·d empagliflozin group, 3mg / kg·d enpagliflozin group, 3mg / kg·d enpagliflozin group The Gliflozin group and the 6mg / kg·d Empagliflozin group were intervened for 3 days. A peritoneal equilibration test (PET) was performed 4 hours before sacrifice. At the end of the experiment, the peritoneal dialysis fluid and blood samples were collected to detect the rat peritoneal dialysis fluid and blood glucose levels, and calculate the ultrafiltration volume and glucose transport volume of the rats.

[0055] The test results showed that: (1) Before PET, compared with the ...

Embodiment 3

[0069] This example discusses the influence of SGLT2 inhibitors on the absorption of glucose by human PMCs, specifically:

[0070] 1. Effect of high sugar and empagliflozin on the activity of PMCs

[0071] The medium containing 60mM glucose (high sugar) and the medium containing 60mM glucose (high sugar) + 1μM empagliflozin were respectively stimulated to the aforementioned PMCs for 0 / 2 / 12 / 24 / 48h, and Annexin V / PI double staining flow was used respectively. Cell viability was detected by cytometry and LDH cytotoxicity assay. Among them, the detection results of Annexin V / PI double staining flow cytometry are as follows: Figures 12A-12Cshown. According to the results shown in Figure 12, compared with the number of apoptotic cells at 0h, the number of total apoptotic cells in PMCs stimulated by high glucose or high glucose + 1 μM empagliflozin for 48 hours was significantly increased (P Figure 13A ~ Figure 13B The results shown show that, compared with the LDH activity of 0h ...

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Abstract

The present invention relates to the application of SGLT2 inhibitors in the preparation of reagents for inhibiting the absorption of glucose by PMCs or peritoneal fibrosis. The reagent prepared by the application of the invention can effectively reduce the transport and consumption of glucose by PMCs in a high glucose state, thereby reducing the absorption of PDS glucose in the peritoneum and increasing the amount of ultrafiltration in the peritoneum, thereby inhibiting or delaying the peritoneal fibrosis and improving the peritoneal fibrosis. Function.

Description

technical field [0001] The invention relates to the field of peritoneal dialysis, in particular to the application of SGLT2 inhibitors in the preparation of reagents for inhibiting the absorption of glucose by PMCs or peritoneal fibrosis. Background technique [0002] Peritoneal dialysis (PD) has become an important part of the integrated treatment of end-stage renal disease (ESRD). At present, about 11% of ESRD patients worldwide choose PD treatment. [0003] The structural and functional integrity of the peritoneum is a necessary condition for PD. Ultrafiltration failure caused by peritoneal fibrosis is the main reason for PD patients to stop dialysis treatment. Previous studies have shown that the incidence of peritoneal fibrosis after 1-2 years of PD treatment is 50%-80%. Therefore, prevention and treatment of peritoneal fibrosis is the key to maintaining the sustainable development of PD, and it is also a research hotspot today. Unfortunately, the current various drug...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/351A61P13/12
CPCA61K31/351A61P13/12
Inventor 周莹陈朝生郑尘非章建娜苏波峰范瑾瑾吴海珊尹沛然郭琳
Owner THE FIRST AFFILIATED HOSPITAL OF WENZHOU MEDICAL UNIV
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