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Application of acetylcysteine in preparation of medicines for preventing and treating postoperative cognitive dysfunction and blood-brain barrier damage mediated encephalopathy

A technology of acetylcysteine ​​and cognitive dysfunction, applied in the treatment of memory function after anesthesia and surgical shock, the field of new object exploration desire decline, to achieve the effect of rich sources

Inactive Publication Date: 2017-06-13
XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since MMP-9 inhibitors are used as experimental reagents, they are still far away from clinical application, so it is urgent to find a special "old drug" to benefit existing patients
[0009] However, since MMP-9 inhibitors are still far away from clinical application as experimental reagents, drugs that use the same mechanism of action to be applied to diseases such as postoperative cognitive impairment mediated by the blood-brain barrier are urgently needed

Method used

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  • Application of acetylcysteine in preparation of medicines for preventing and treating postoperative cognitive dysfunction and blood-brain barrier damage mediated encephalopathy
  • Application of acetylcysteine in preparation of medicines for preventing and treating postoperative cognitive dysfunction and blood-brain barrier damage mediated encephalopathy
  • Application of acetylcysteine in preparation of medicines for preventing and treating postoperative cognitive dysfunction and blood-brain barrier damage mediated encephalopathy

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] It is reasonable to speculate that MMP-9 or MMP-2 may be an important factor that mediates endothelial cell damage in the process of PCOD and leads to the pathogenesis of POCD. In response to this speculation, the important role of MMP-9 and MMP-2 in the pathogenesis of POCD was demonstrated in detail in the early stage. The results of the experiment found that surgery and anesthesia trauma can trigger peripheral blood MMP-9, rather than MMP-2, to rapidly and strongly increase during the pathogenesis of POCD ( figure 1 ); and lead to the dysfunction of microvascular endothelial cells in the brain. Intravenous injection of MMP-9 inhibitors to mice in advance can significantly alleviate the decline in fear memory ability and new object recognition ability caused by surgical anesthesia trauma ( figure 1 ). This shows that the up-regulation of MMP-9 levels induced by anesthesia and surgery plays an important role in the impairment of cognitive function.

[0040] The spec...

Embodiment 2

[0050] N-acetylcysteine ​​is a kind of mucolytic agent, and it can also be used as an antidote for acetaminophen. It is also clinically used for the treatment of renal idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and so on. More importantly, acetylcysteine ​​has an excellent safety history, and its abundant cysteine ​​residues have great potential for interfering with the "cysteine ​​switch" in the activation process of matrix metalloproteinases.

[0051] Matrix metalloproteases contain a unique structure called a "cysteine ​​switch". The cysteine ​​switch consists of 2 key parts; one is the cysteine ​​residue in the peptide domain, and the other is the zinc binding in the catalytic domain location. When cysteine ​​residues are modified by S-nitrosylation, oxidation, and alkylation, they will dissociate from the cysteine ​​residues at the zinc binding site, resulting in the activation of matrix metalloproteinases. Therefore, modification of cysteine ​​...

Embodiment 3

[0065] Animals were subjected to intravenous injection of MMP-9 inhibitors to determine the effects of surgical anesthesia trauma on blood-brain barrier permeability and hippocampal IL-1β levels in mice. The experimental results showed that compared with the simple surgical trauma group, the surgical Pre-injection of MMP-9 inhibitors can significantly reduce the leakage of the blood-brain barrier and the increase of hippocampal IL-1β levels in surgery-induced mice.

[0066] The specific test content is as follows.

[0067] a) Test animals:

[0068] Healthy male C57BL / 6J, 12-14 3-3.5 month old mice, clean grade. The experimental animals were raised in an independent environment with 12h-12h alternation of day and night, the room temperature was maintained at 24±2°C, water and food were free to drink, and the experiment was carried out after 1 week of adaptation to the environment.

[0069] b) Drugs and reagents

[0070] DMSO, Inc., method of formulation; MMP-9 Inhibitor, Inc...

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Abstract

The invention discloses application of acetylcysteine in preparation of medicines for preventing and treating postoperative cognitive dysfunction and blood brain-barrier damage mediated encephalopathy and specifically discloses application of acetylcysteine in treatment of cognitive impairment after anesthesia and surgical trauma. Due to advanced application of the acetylcysteine before operative anesthesia, reduction of fear memory ability and new object recognition ability related to hippocampus after the anesthesia and operation can be obviously alleviated. The effect is specifically achieved by inhibiting a level of peripheral matrix metalloproteinase-9 through the acetylcysteine to protect the blood brain-barrier function and reducing the inflammatory factor up-regulation level of the hippocampus.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to the new application of acetylcysteine ​​in the field of drugs for treating postoperative cognitive dysfunction, in particular to the application in the treatment of memory function and decreased desire to explore new objects after anesthesia and surgical shock. Background technique [0002] Postoperative cognitive dysfunction (POCD, Postoperative Cognitive Dysfunction) is considered to be the central nervous system dysfunction caused by anesthesia, surgery and other factors. [0003] Postoperative cognitive dysfunction (POCD) is the central nervous system (CNS, Central Nervous System) degeneration induced by anesthesia and surgical trauma on the basis of central nervous system dysfunction, the current experimental research mainly focuses on the activation of central nervous system inflammation The final impact on the central nervous system focuses on the downstream terminal manifestations o...

Claims

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Application Information

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IPC IPC(8): A61K31/198A61P25/28
CPCA61K31/198
Inventor 韩园高灿刘文涛陈文裕
Owner XUZHOU MEDICAL UNIV
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