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Application of tifa inhibitor in the preparation of medicine for treating and/or preventing sepsis acute kidney injury

A technology for acute kidney injury and sepsis, applied in the field of biomedicine, can solve the problem of non-specific treatment of sepsis AKI, and achieve the effect of reducing cell pyroptosis

Active Publication Date: 2022-07-05
ZHONGNAN HOSPITAL OF WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no specific treatment for sepsis AKI

Method used

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  • Application of tifa inhibitor in the preparation of medicine for treating and/or preventing sepsis acute kidney injury
  • Application of tifa inhibitor in the preparation of medicine for treating and/or preventing sepsis acute kidney injury
  • Application of tifa inhibitor in the preparation of medicine for treating and/or preventing sepsis acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1. TIFA is used as molecular marker to prepare sepsis kidney injury detection kit

[0039] 1. Screening and analysis of DEGs between sepsis-induced AKI group and control group

[0040] (1) Construction of sepsis AKI mouse model

[0041] Constructing the sepsis AKI mouse model: The acute kidney injury model of sepsis was induced by the method of CLP, as follows: 8-12-week-old C57BL / 6 male mice were selected. After anesthetizing the mice, the abdominal cavity was opened, and 1 / 1 4-length cecum, pierce 2 holes in the cecum with a 22G needle, squeeze out the stool, close the abdominal cavity layer by layer, and perform fluid resuscitation (see Peng ZY, et al. Crit Care Med. 2012 Feb; 40(2): 538-43). The control group was not subjected to cecal ligation and perforation, and the rest of the steps were the same.

[0042] (2) Serum creatinine (Scr) detection

[0043] Serum was collected 24 hours after CLP, and serum creatinine (Scr) was detected using a creatinine d...

Embodiment 2

[0100] Example 2. Application of TIFA as a target in the preparation of a drug for the treatment and / or prevention of sepsis acute kidney injury

[0101] 1. An siRNA involving silencing of TIFA, the nucleotide sequence of the siRNA is shown in SEQ ID NO:1.

[0102] siRNA: 5'-GAGCTGGGCTACCTAAATA-3'.

[0103] 2. To further study the role of TIFA in sepsis, HK-2 cells were transfected with the TIFA siRNA. The mRNA and protein levels of TIFA were detected by the method described in Example 1;

[0104] The result is as Figure 5 As shown in A and 5B, it was found that the mRNA and protein levels of TIFA were significantly reduced.

[0105] 3. Evaluation of mitochondrial membrane potential

[0106]HK2 cells were added with pre-warmed CM, 4 μM of the potentially sensitive dye JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzene-imidazolyl-carbon cyanine iodide, Yeasen, Inc., Cat#40706ES60), and the cells were returned to the incubator. After 15 minutes, they were washed twic...

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Abstract

The present invention provides the use of TIFA as a target in the preparation of a medicament for treating and / or preventing sepsis acute kidney injury. This application found that the expression of TIFA was significantly increased in septic kidney injury, and the specific siRNA sequence was used to efficiently inhibit the expression of TIFA gene in human renal tubular epithelial cell lines. By inhibiting the expression of cytokines, flow cytometry showed that si-TIFA could restore mitochondrial transmembrane potential and reduce pyroptosis in HK-2 cells. It can be seen that the silencing of the TIFA gene of the present invention can be used as a new target in the preparation of medicines for improving sepsis-induced renal injury, which solves the key problem of target treatment of sepsis-induced AKI, and is a method for preparing sepsis-induced AKI. Drugs for AKI provide the basis.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of TIFA as a target in the preparation of a medicament for treating and / or preventing sepsis acute kidney injury. Background technique [0002] Acute kidney injury (AKI) is a rapid loss of renal function caused by multiple etiologies, and AKI is an independent risk factor for death from sepsis. Sepsis accounts for 45%-70% of all AKI cases. To date, there is no specific treatment for septic AKI. Therefore, there is an urgent need to develop new and more specific drugs for the treatment of sepsis AKI. [0003] Pyroptosis is a protective inflammatory response to cellular damage (host defense and repair), and an excessive inflammatory response can exacerbate kidney damage. Inflammasome activation occurs both in immune cells (mainly macrophages and dendritic cells) and in some innate renal cells (eg, renal tubular epithelial cells). The biochemical characterist...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/7088A61P13/12C12Q1/6883
CPCA61K45/00A61K31/7088A61P13/12C12Q1/6883C12Q2600/158Y02A50/30
Inventor 李一鸣彭志勇张婧锁进猛徐冬雪姜军
Owner ZHONGNAN HOSPITAL OF WUHAN UNIV
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