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Pharmaceutical composition for treating type 2 long QT syndrome and application thereof

A technology of QT syndrome and composition, applied in the field of medicine, can solve problems such as complex pathogenesis, and achieve the effect of increasing current density

Inactive Publication Date: 2021-12-07
NINGBO MEDICAL CENT LIHUILI HOSPITACL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the complex pathogenesis, the treatment of LQT2 still faces severe challenges
Although the application of β-receptor antagonists and the implantation of cardioverter-defibrillator (ICD) have certain effects on preventing fatal arrhythmias in high-risk patients, none of these treatments can fundamentally correct the transport of hERG and produce a radical effect

Method used

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  • Pharmaceutical composition for treating type 2 long QT syndrome and application thereof
  • Pharmaceutical composition for treating type 2 long QT syndrome and application thereof
  • Pharmaceutical composition for treating type 2 long QT syndrome and application thereof

Examples

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Embodiment 1

[0021] Cell culture and construction of hERG translocation disorder model: by transient transfection, pcDNA3-Mock, pcDNA3-HERG, pcDNA3-HERG / pcDNA3-HERG-A561V, pcDNA3-HERG-A561V plasmids were transfected to produce control, wild, heterozygous and HEK293 cell line with mutated hERG. The above cells were cultured in DMEM (high glucose) containing 10% fetal bovine serum, and maintained in an incubator environment at 37° C. containing 5% carbon dioxide. Cells were harvested from the dish, resuspended as single cells and cultured in small dishes of fresh MEM for at least 4 hours before use.

[0022] Quantitative RT-PCR: Cells before and after drug treatment were lysed with TransZol Up (whole gold) and total RNA was extracted, reverse-transcribed into cDNA, and 1 μg was used as a template, configured according to the 2×T5 Fast qPCR Mix (Qingke Bio) The 20 μl reaction system was used to detect the expression of the target gene, and SYBR Green I was used as the expression signal. Duri...

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Abstract

The invention belongs to the field of medicines, and relates to a pharmaceutical composition for treating type 2 long QT syndrome and application thereof. According to the invention, immunoblotting detection is utilized to find that the combined application of the Lurmacatray and the HSF1A has an obvious promotion effect on mature transport of hERG mutant protein, the Lurmacatray and the HSF1A are applied to an HEK-293 cell model transfecting hERG and mutant plasmids of the hERG, and Ikr current generated by an hERG channel is detected by utilizing whole-cell patch forceps, so that the combined application of the Lurmacatray and the HSF1A finds that the current density is obviously increased, and activation gating kinetics of a mutation channel is converted into a wild type, so that the transport of the hERG mutant protein is realized by up-regulating key transport molecular chaperones Hsp70 and Hsp90 by utilizing the combination of the Lurmacatray and the HSF1A, and the aim of treating the type 2 long QT syndrome is fulfilled by promoting the mature transport of the hERG mutant protein.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a pharmaceutical composition for treating type 2 long QT syndrome and its application. Background technique [0002] Congenital long QT syndrome (LQTS) is an inherited cardiac ion channelopathy caused by mutations in 15 autosomal dominantly related genes, clinically divided into 17 subtypes, characterized by QT Prolonged intervals and arrhythmias associated with emotions, stress, etc. Long QT syndrome type 2 (LQT2), the most common subtype in my country, is caused by mutations in KCNH2 (also known as hERG) that cause rapid activation of the 3-phase repolarization of the cardiac action potential delayed rectifier potassium current I kr caused by the reduction. [0003] The intracellular maturation of hERG channel proteins requires the assistance of many molecular chaperones, especially the heat shock proteins Hsp70 and Hsp90 in the cytoplasm, and related stress proteins in the endoplasmic ...

Claims

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Application Information

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IPC IPC(8): A61K31/443A61K31/4155A61P9/06
CPCA61K31/443A61K31/4155A61P9/06A61K2300/00
Inventor 廉姜芳杨曦郑泽群黄晓燕宋勇飞袁园
Owner NINGBO MEDICAL CENT LIHUILI HOSPITACL
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