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Applications of calpain inhibitor in preparing drugs for treating acute kidney injury caused by endotoxin

A kind of acute kidney injury and calpain technology, which can be used in drug combinations, pharmaceutical formulations, organic active ingredients, etc., can solve the problems of difficult intervention measures and incompletely clear mechanisms, and can inhibit endothelial cell apoptosis, reduce iNOS expression and NO. and the effect of ROS

Inactive Publication Date: 2020-05-29
GENERAL HOSPITAL OF SOUTHERN THEATRE COMMAND OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, endothelial cells play an important role in acute kidney injury caused by sepsis, and the mechanism of endothelial cell injury in sepsis is not yet fully understood, which makes it difficult to formulate targeted interventions

Method used

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  • Applications of calpain inhibitor in preparing drugs for treating acute kidney injury caused by endotoxin
  • Applications of calpain inhibitor in preparing drugs for treating acute kidney injury caused by endotoxin
  • Applications of calpain inhibitor in preparing drugs for treating acute kidney injury caused by endotoxin

Examples

Experimental program
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Embodiment Construction

[0016] Materials and methods

[0017] A pair of C57BL / 6 mice were purchased from the Jackson laboratory, and Dr Laurent Baud of Notre Dame de Paris, France, provided transgenic mice overexpressing calpastatin (Tg-CAST). Transgenic mice with endothelial cell-specific Capn4 knockout (TEK / Capn4- / -) and lymphocyte-specific Capn4 knockout (LYZ / Capn4- / -) were purchased from Jackson Laboratories and maintained at our Animal Care The institution operates a breeding program.

[0018] All animals were provided with food and water on a regular basis and housed in a temperature- and humidity-controlled facility with a 12-h light and dark cycle. The Use of Animals Subcommittee at Western University approved all experimental protocols and all animals were used in accordance with the guidelines of the Canadian Council on Animal Care.

[0019] Establishment of animal model of endotoxemia

[0020] According to our previous research, the animal model of endotoxemia was prepared with LPS (4mg...

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Abstract

The invention discloses applications of a calpain inhibitor in preparing drugs for treating acute kidney injury caused by endotoxin. In applications, the calpain inhibitor can protect acute kidney injury caused by endotoxin by inhibiting endothelial cell calpain. Through the using of the calpain inhibitor and the combined using of multiple cell-specific calpain knockout mice, the effects and possible mechanism of action of the endothelial cell calpain in the acute kidney injury can be researched, and the possibility of taking the calpain inhibitor III as a treatment option can be researched aswell; and after the calpain inhibitor is applied to inhibit the activity of the calpain, p38 phosphorylation can be inhibited so as to reduce iNOS expression and the generation of NO and ROS, and endothelial cell apoptosis can also be inhibited so as to achieve protective effects in the renal injury caused by LPS.

Description

technical field [0001] The invention relates to the application of a calpain inhibitor in the preparation of a medicine for treating acute kidney injury caused by endotoxin. Background technique [0002] Acute kidney injury is one of the common complications in intensive care unit patients, among which sepsis is an important cause of acute kidney injury. In the state of sepsis, many factors can lead to acute kidney injury, including: hemodynamic instability, microcirculation disturbance, endothelial injury, etc. Under normal circumstances, the kidneys can accept 20% of the cardiac output, and the abundant capillaries in the kidneys play an important role in maintaining the glomerular filtration rate. Vascular endothelial cells play an important role in maintaining body homeostasis and the blood-kidney barrier. In sepsis, vascular endothelial cells are exposed to many stimuli, including endotoxins, inflammatory factors, and others. Structural changes in the vascular endoth...

Claims

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Application Information

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IPC IPC(8): A61K31/222A61P13/12
CPCA61K31/222A61P13/12
Inventor 刘志锋吉晶晶苏磊
Owner GENERAL HOSPITAL OF SOUTHERN THEATRE COMMAND OF PLA
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