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Application of TRPV4 ion channel as drug target in organophosphorus compound poisoning

An ion channel and organophosphate technology, applied in the field of medicine, can solve problems that have not been reported or applied

Active Publication Date: 2020-10-23
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] At present, there are no reports or applications of TRPV4 as a drug target in organophosphorus compound poisoning at home and abroad

Method used

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  • Application of TRPV4 ion channel as drug target in organophosphorus compound poisoning
  • Application of TRPV4 ion channel as drug target in organophosphorus compound poisoning
  • Application of TRPV4 ion channel as drug target in organophosphorus compound poisoning

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Embodiment Construction

[0022] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0023] 1. Experimental materials

[0024] 1.1 Experimental animals: SD male rats and 17-18-day pregnant female rats were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

[0025] 1.2 TRPV4 antagonist GSK2193874 was purchased from Selleck Company; TRPV4 siRNA and transfection reagent were purchased from Invitrogen Company of the United States; anti-TRPV4 antibody was purchased from ThermoFisher Company of the United States; anti-ACTB antibody and anti-p-NMDAR2B antibody were purchased from CST Company of the United States; MTT reagent The box and BCA protein quantification kit were purchased from Nanjing Jiancheng Institute of Bioengineering; Fura-4AM was purchased from Invitrogen Corporation of the United States.

[0026] 2. Experimental method

[0027] 2.1 Establishment of organophosphorus co...

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Abstract

The invention discloses an application of a TRPV4 ion channel as a drug target in organophosphorus compound poisoning. A medicine is a TRPV4 inhibitor. The medicine comprises: pharmacological antagonists of TRPV4 including GSK2193874, HC-067047, GSK205, GSK3395879, RN-1734 and GSK2798745, a blocking type antibody of the TRPV4, siRNA of the TRPV4 and the like. The important point of the invention is that the TRPV4 is found to be closely related to brain injury caused by the organophosphorus compound poisoning; and the TRPV4 antagonists or the siRNA inhibits intracellular calcium flow caused bythe organophosphorus compound poisoning and NMDA receptor-mediated excitatory toxicity, so that the nervous system toxic effect induced by poisoning of two organophosphorus compounds including oxophosphorus and soman is remarkably reduced at both in-vivo and in-vitro levels. Therefore, the invention provides a new drug target for prevention and treatment of the organophosphorus compound poisoning,and provides a new strategy for clinical treatment of the organophosphorus compound poisoning.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of TRPV4 ion channel as a drug target in organophosphorus compound poisoning. Background technique [0002] Organophosphorus compounds are widely used in agricultural and military fields. This type of compound inhibits the activity of acetylcholinesterase, resulting in the excessive accumulation of acetylcholine in the body, which causes severe dysfunction of the central and peripheral cholinergic nervous system, and at the same time disrupts the excitatory neurotransmitter system and triggers inflammatory reactions in the later stage, eventually leading to severe Brain Injury. Common organophosphorus compounds can be divided into military nerve agents (nerve agents) and organophosphate pesticides (organophosphate pesticides, OPS) according to their uses. Among them, military nerve agents are represented by tabun, sarin, soman and Viex (VX), which have been used many tim...

Claims

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Application Information

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IPC IPC(8): C12Q1/02G01N33/68A61K45/00A61P39/02
CPCA61K45/00A61P39/02G01N33/5014G01N33/6893G01N2800/28
Inventor 骆媛王永安王帅隋昕杨军杨扬乔思默
Owner ACADEMY OF MILITARY MEDICAL SCI
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