Application of tyrosine kinase inhibitor as treatment drug for acute kidney injury

A technology for acute kidney injury and tyrosine kinase, which can be used in drug combinations, pharmaceutical formulations, organic active ingredients, etc., to solve problems such as unclear regulatory mechanisms and elevated levels of PDCD4 expression in the kidneys

Active Publication Date: 2019-12-06
SHANDONG UNIV
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  • Application Information

AI Technical Summary

Problems solved by technology

Existing studies have shown that the expression level of PDCD4 in the kidney is significantly increased after AKI, suggesting that it plays an important role in the pathophysiological process of AKI, but its exact regulatory mechanism is not clear

Method used

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  • Application of tyrosine kinase inhibitor as treatment drug for acute kidney injury
  • Application of tyrosine kinase inhibitor as treatment drug for acute kidney injury
  • Application of tyrosine kinase inhibitor as treatment drug for acute kidney injury

Examples

Experimental program
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Effect test

Embodiment 1

[0108] 1. Experimental steps

[0109] 1. Expression distribution and role of PDCD4 in renal ischemia-reperfusion injury

[0110] 1.1 The expression changes and role of PDCD4 in ischemia-reperfusion injury

[0111] 1.1.1 Establish a mouse model of renal ischemia-reperfusion injury and detect the expression changes of PDCD4

[0112] 12-week-old C57BL / 6J male mice were selected to establish an acute renal ischemia-reperfusion model, and real-time fluorescent quantitative PCR (Real-time RT-PCR), WB, and immunohistochemical staining (Immunohistochemical–staining, IHC) were used to detect PDCD4 in The expression changes of mRNA and protein levels at different time points after ischemia-reperfusion, namely 24h, 48h, and 72h. At the same time, the expression distribution of PDCD4 in the proximal convoluted tubule, distal convoluted tubule and collecting duct of the kidney and the expression change of renal ischemia-reperfusion injury were detected by immunofluorescence (Immunofluore...

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Abstract

The invention belongs to the technical field of kidney injury treatment drugs, and particularly relates to application of ponatinib as a drug for acute kidney injury. As an acute clinical complication, the acute kidney injury has the characteristics of being high in morbidity and high in mortality, and effective treatment drugs are not achieved at present. Related researchers in the field show that PDCD4 expression becomes higher in an acute kidney injury model, and it is indicated that the PDCD4 plays an important role in the physiological mechanism related to the acute kidney injury. The situation that the PDCD4 aggravates the kidney injury by regulating an Fgr-Stat3-Notch1 pathway is further confirmed. The confirmation of the regulatory mechanism provides a basis for the treatment of the acute kidney injury. According to the research results, the ponatinib, an Fgr kinase inhibitor, is adopted to treat the acute kidney injury, the drug has a significant protective effect on the injury caused by kidney ischemia reperfusion, and it is indicated that the drug intervention in Fgr can prevent and treat the acute kidney injury.

Description

technical field [0001] The disclosure belongs to the technical field of drugs for treating acute kidney injury, and in particular relates to the application of tyrosine kinase inhibitors as drugs for acute kidney injury. Background technique [0002] The information disclosed in this Background section is only intended to increase the understanding of the general background of the disclosure, and is not necessarily to be taken as an acknowledgment or any form of suggestion that the information constitutes prior art that is already known to those skilled in the art. [0003] Acute Kidney Injury (AKI) is a serious clinical complication with rapid onset and rapid progress, and it is also an important cause of chronic renal failure. In severe cases, it can develop into systemic complications such as uremia, and has high Characterized by morbidity and high mortality. Clinically, it is usually caused by ischemia / reperfusion injury (IRI), sepsis or chemotherapy drugs, etc. Althoug...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5025A61P13/12
CPCA61K31/5025A61P13/12
Inventor 张艳高飞易凡彭涛任丹丹靖旭韩庆胜
Owner SHANDONG UNIV
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