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Application of hydrogen sulfide slow-release organic donor ADT-OH in preparation of medicine for treating nervous system diseases

A technology for neurological diseases and therapeutic drugs, applied in the field of biological cytology and regenerative medicine, can solve the problem of unclear potential effects of neural precursor cell differentiation, and achieve the effect of reducing the number of deaths

Active Publication Date: 2021-11-26
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the potential effect of ADT-OH on the differentiation of neural progenitor cells is unclear

Method used

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  • Application of hydrogen sulfide slow-release organic donor ADT-OH in preparation of medicine for treating nervous system diseases
  • Application of hydrogen sulfide slow-release organic donor ADT-OH in preparation of medicine for treating nervous system diseases
  • Application of hydrogen sulfide slow-release organic donor ADT-OH in preparation of medicine for treating nervous system diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] (1) Male and female adult ICR mice were randomly mated at a ratio of 2:1. Every night at 8 o'clock, male and female mice were caged together. On the second day, if the female mouse had a vaginal plug at 8 o'clock in the morning, it indicated that the mating was successful, and this day was recorded as the first day of the mouse's pregnancy. When the mouse is 14.5 days pregnant (E14.5), it can be used for the extraction of neural precursor cells.

[0032]C57BL / 6J mice pregnant for 14.5 days were anesthetized by intraperitoneal injection of 4% chloral hydrate, the abdominal cavity of the pregnant mice was opened with sterile surgical scissors and surgical forceps, the uterus of the pregnant mice was dug open, and the brains of the fetal mice were taken out. Separate the fetal mouse brain tissue in the subventricular zone, digest the tissue with 0.05% trypsin in a 37°C water bath for 10 minutes, and then use the neural precursor cell culture medium (DMEM-F12 medium 39.2ml...

Embodiment 2

[0042] After the primary isolated neural precursor cells were cultured for 3-4 days, the neurospheres were blown into single cells and seeded in a 24-well cell culture plate covered with adhesive slides. The cells were added with ADT-OH (80 μmol / L ) and the control solute DMSO in the neural precursor cell culture medium for 3 days, then stained with the apoptosis-specific antibody caspase3, collected pictures under a fluorescent microscope, and counted the ratio of caspase3 positive cells to all DAPI positive cells. The statistical results showed that, and DMSO Compared with the control group, the ADT-OH group had fewer cells undergoing apoptosis ( Figure 4 A and B), the above data show that ADT-OH can protect neural precursor cells from apoptosis.

[0043] In summary, compared with the DMSO control group, the neuron differentiation rate in the ADT-OH group increased by 57.69%, the oligodendrocyte differentiation rate increased by 87.5%, and the astrocyte differentiation rate...

Embodiment 3

[0045] A mouse model of spinal cord injury was established by dropping a heavy object onto the dorsal side of the spinal cord of the mouse. The specific operations were as follows: the mouse was anesthetized, the back was cut in the middle, the lamina was removed, and the spinal dura mater was exposed; the heavy object was dropped from a certain height Fall freely and hit the spinal cord, causing spinal cord injury. Afterwards, the neural precursor cells treated with ADT-OH drugs were transplanted into the spinal cord injury site under a stereomicroscope, and the differentiation, cell survival and axon growth of the neural precursor cells in the injured site were detected one month later to evaluate the spinal cord repair. Effect.

[0046] The results showed that one month after the implantation of neural precursor cells treated with ADT-OH drug, the number of neurons and oligodendrocytes in the mouse spinal cord injury site greatly increased, and the number of astrocytes was ...

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Abstract

The invention relates to an application of a hydrogen sulfide slow-release organic donor ADT-OH drug in neural precursor cell differentiation, and the substance can induce more directional differentiation of neural precursor cells into neurons and oligodendrocytes and less differentiation into astrocytes, promote the axon growth of neurons, promote the apoptosis of neurons. Meanwhile, the death number of the neural precursor cells can be reduced, a direction is provided for repairing damaged nerves by transplanting the neural precursor cells, and ADT-OH is likely to become a new drug target for clinically treating nervous system diseases.

Description

technical field [0001] The invention relates to the fields of biological cytology and regenerative medicine, in particular to the application of a hydrogen sulfide slow-release organic donor ADT-OH in the preparation of drugs for the treatment of nervous system diseases. Background technique [0002] Neural stem cells, also known as neural precursor cells (NPCs), are cells with multilineage differentiation potential. During the development of the central nervous system (CNS), the subventricular zone is the main distribution area of ​​NPCs. NPCs can divide symmetrically to maintain their own cell numbers, and can also divide asymmetrically to generate neurons, astrocytes, and oligodendrocytes. In the mammalian nervous system, neurons are terminally differentiated cells that cannot re-divide and produce new cells, so neurons cannot be replenished after death. The low number of neural stem cells in the adult mammalian nervous system is generally insufficient to compensate for...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/385A61P25/00C12N5/079C12N5/0793
CPCA61K31/385A61P25/00C12N5/0619C12N5/0622C12N2501/999Y02A50/30A61K35/30C12N2513/00C12N2506/08C12N2501/11C12N2501/119
Inventor 马艳霞韦善文邹明明倪莉周立宇李迪杨严伟
Owner SUZHOU UNIV
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