Application of bromodomain protein 4 (BRD4) inhibitor JQ1 or derivative thereof in preparation of medicine for treating sepsis intestinal barrier injury

A barrier damage and inhibitor technology, applied in the field of medicine, can solve problems such as unreported application of JQ1

Active Publication Date: 2020-08-14
THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no report on the application of JQ1 in the treatment of intestinal barrier damage in sepsis

Method used

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  • Application of bromodomain protein 4 (BRD4) inhibitor JQ1 or derivative thereof in preparation of medicine for treating sepsis intestinal barrier injury
  • Application of bromodomain protein 4 (BRD4) inhibitor JQ1 or derivative thereof in preparation of medicine for treating sepsis intestinal barrier injury
  • Application of bromodomain protein 4 (BRD4) inhibitor JQ1 or derivative thereof in preparation of medicine for treating sepsis intestinal barrier injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The animals selected for this experiment were 8-week-old C57BL / 6 male mice, weighing about 25 grams, purchased from Hunan Slack Jingda, license number: SCXK (Xiang) 2019-0004, and the mice were placed in an artificial day and night cycle lighting environment for 12 hours Raised in the middle, free access to food and water. C57BL / 6 male mice were randomly divided into normal saline control group (5 mice), LPS modeling group (10mg / kg, 5 mice), JQ1 administration group (50mg / kg, 5 mice). Injection of corresponding doses of normal saline or JQ1 drugs, intraperitoneal injection of 10mg / kg LPS 1h later, 24h later (starting timing after LPS injection), anesthetized mice with 4% chloral hydrate intraperitoneal injection, after complete anesthesia, intestinal tissue was taken and placed in Fix in 4% paraformaldehyde overnight for tissue HE staining.

[0036] Intestinal tissue HE staining steps:

[0037] (1) The fixed intestinal tissues were dehydrated with graded alcohol, embe...

Embodiment 2

[0045] The source of experimental animals, feeding conditions and administration process are all referred to Example 1. After the mice were anesthetized, the intestinal tissues were taken and stored at -80°C for fluorescent quantitative PCR detection.

[0046] Intestinal tissue fluorescent quantitative PCR steps:

[0047] (1) RNA extraction and reverse transcription: Homogenize the tissue with 1ml Trizol lysate, add 200μl chloroform, mix well and let stand for 5min; centrifuge at 12000g for 15min at 4°C, transfer the upper aqueous phase, add an equal volume of isopropanol and mix well centrifuge at 12000g for 10min at 4°C; discard the supernatant and add 1ml of 75% ethanol; centrifuge at 7500g for 5min at 4°C and discard the supernatant; add 20 μl of enzyme-free water to dissolve after drying; : K1621) instructions for reverse transcription of RNA into cDNA.

[0048] (2) RT-PCR: 10 μl reaction system: 5 μl TB reaction solution, 0.2 μl ROX dye, 0.4 μl each of upstream and dow...

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Abstract

The invention relates to the technical field of medicines, in particular to an application of a bromodomain protein 4 (BRD4) inhibitor JQ1 or a derivative thereof in preparation of a medicine for treating sepsis intestinal barrier injury. Experiments show that in a lipopolysaccharide (LPS)-induced sepsis mouse intestinal barrier injury model, the BRD4 inhibitor JQ1 can effectively inhibit LPS-induced sepsis mouse intestinal mucosa damage, release of inflammatory factors TNF[alpha], IL1[beta] and IL18, release of NLRP3 complex inflammasome, and high expression of pyroptosis marker genes GSDMD,GSDME, P2X7 and Aim2. Results show that the BRD4 inhibitor JQ1 can effectively prevent the sepsis mouse intestinal barrier injury by inhibiting intestinal tissue cell pyroptosis, and can be used for preparing a pharmaceutical preparation for treating the sepsis intestinal barrier injury.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to the application of bromodomain protein 4 (BRD4) inhibitor JQ1 or its derivatives in the preparation of drugs for treating sepsis intestinal barrier damage. Background technique [0002] Sepsis is a systemic inflammatory response syndrome caused by infection. Although great progress has been made in antibiotic treatment and surgical operation, the morbidity and mortality of sepsis are still high. The intestinal tract is one of the earliest organs involved in the onset of sepsis, and its intestinal barrier damage plays an initiating role in the outbreak of sepsis infection. In severe sepsis, the intestinal mucosa is damaged and the permeability increases. A large number of bacteria and endotoxins enter the blood and lymphatic circulation system, and activate and release various inflammatory factors such as TNFα and IL1, which eventually lead to multiple organ dysfunction througho...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/551A61P1/04
CPCA61K31/551A61P1/04
Inventor 陈玲李威钟小林杨惠曹文宇徐杨毛明莉李梦琳时萌萌张圆
Owner THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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