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New uses of bk channel openers

A channel and action technology, applied in the field of BK channel openers

Active Publication Date: 2020-12-11
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Both NS1619 and BMS191011 are BK channel openers, and there is no report on the inhibitory effect of BK channel openers on renal fibrosis

Method used

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  • New uses of bk channel openers
  • New uses of bk channel openers
  • New uses of bk channel openers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] 1.1 Test materials: methanol (Sinopharm Chemical Reagent Co., Ltd.), paraformaldehyde (Sinopharm Chemical Reagent Co., Ltd.), ethanol (Sinopharm Chemical Reagent Co., Ltd.), cell culture medium: RPMI 1640 medium, DMEM medium (Gibco ), Fetal Bovine Serum (Gibco), PBS Phosphate Buffered Saline, Trypsin (Gibco), TGF-β1 (R&D), DMSO (Sigma), Page Ruler TMPrestmned Protein Ladder (Fermen tas) Mouse monoclonal toalpha muscle Actin (Abcam), E-cadhefin rabbit monoclonal antibody (Epitomics), PAl-1rabbit monoclonal antibody (Epitomics), HRP-labeled goat anti-rabbit IgG (H+L), HRP-labeled goat Anti-mouse IgG (H+L) (Mingrui Biotechnology), beta-Actin antibody (Sigma), BSA (Sigma), hydrogen peroxide (Sinopharm Chemical Reagent Co., Ltd.), hematoxylin stain (Wuhan Google Biotechnology Co., Ltd.), Hydrochloric acid, ammonia water (Sinopharm Chemical Reagent Co., Ltd.), neutral gum (Google Bio).

[0049] 1.2 Main instruments and equipment: Ultra-clean workbench Suzhou Purification Equ...

Embodiment 2B

[0066] Example 2 BK channel opener BMS191011 inhibits folic acid-induced renal fibrosis in mice

[0067] This example discloses the experiment of BK channel opener BMS191011 inhibiting folic acid-induced renal fibrosis in mice. The specific steps are as follows:

[0068] All experiments were approved by the Animal Care and Use Committee of Shanghai Medical College, Fudan University. The present invention uses male adult C57 mice (provided by Animal Experiment Center, School of Pharmacy, Fudan University, Shanghai, China).

[0069] 2.1 Grouping: Take 8-week-old C57 mice, weighing 20-22 g, and divide them into control group (CON group), FAN group, BMS191011 group and FAN+BMS191011 group, with 5 mice in each group.

[0070] 2.2 Modeling: FAN group and FAN+BMS191011 group were intraperitoneally injected with 25 mg / kg folic acid to make models. On the first day of modeling, the BMS191011 group and the FAN+BMS191011 group were intraperitoneally injected with 10 mg / kg of BMS191011,...

Embodiment 3B

[0074] Example 3 BK channel opener NS1619 or BMS191011 inhibits TGF-β1-induced renal fibroblast NRK-49F renal fibrosis cell experiment

[0075] 1. NS1619 inhibits TGF-β1-induced renal fibrosis in rat kidney fibroblasts NRK-49F

[0076] The test steps are as follows:

[0077] Rat kidney fibroblast NRK-49F was inoculated in a well plate, and the cell planting density in each well of the 6-well plate was 30%. After the cells were plated overnight, the cells were cultured in a serum-free medium. The cells were divided into control groups, fibrosis group (TGF-β1 is 10ng / ml), very low-dose administration group (TGF-β1 10ng / ml+NS1619 5μM), low-dose administration group (TGF-β110ng / ml+NS1619 10μM), middle-dose administration group (TGF-β1 10ng / ml+NS1619 20μM), high-dose administration group (TGF-β110ng / ml+NS1619 30μM), after 24 hours of cell culture, add cell lysate, extract cell protein, and use western blot method to detect cells Fibronectin, α-SMA, p-smad2 and GAPDH protein conte...

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Abstract

The invention belongs to the biology field, and particularly relates to a new purpose of a BK channel opener. The BK channel opener is selected from one or combination of two kinds of NS1619 and BMS191011. Through detection of biochemical indicators after an animal model provides BK channel opener NS1619 and BMS191011 intervention, and through in vitro cell research, experiment methods of proteinblot, data analysis and the like can show that the BK channel openers NS1619 and BMS191011 have the effect of restraining renal fibrosis, including the effect of restraining ECM accumulation, the effect of restraining a renal fibrosis marker from being generated, and the effect of restraining a TGF / Smad signal channel. The invention provides a theoretical basis for a mechanism of pharmacological action of restraining renal fibrosis and the like, and also establishes a test foundation for preparation of medicines for treating chronic kidney diseases, and has important significance.

Description

technical field [0001] The invention belongs to the biological field, and in particular relates to a new application of a BK channel opener. Background technique [0002] In recent years, chronic kidney disease (chronic kidney disease, CKD) has shown an increasing trend year by year both at home and abroad, among which the prevalence rate of chronic kidney disease in the adult population in my country is 10.8%. The main causes include chronic glomerulonephritis, hypertensive nephropathy, Diabetic nephropathy, renal interstitial disease, renal tubular disease, congenitally acquired kidney disease, and irrational use of nephrotoxic drugs, etc. The progression of chronic kidney disease (CKD) not only leads to end-stage renal disease (ESRD), but also is a high risk factor for all-cause mortality. The common pathway for the development of chronic kidney disease (CKD) to renal failure (ESRD) caused by various reasons is renal fibrosis, including glomerular fibrosis, renal intersti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P13/12
Inventor 张雪梅王印行辛宏余科王孟玲宁凤玲
Owner FUDAN UNIV