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Application of CDNF (cerebral dopamine neurotrophic factor) in preparation of ischemic cerebrovascular disease drugs

A technology for neurotrophic factors and cerebrovascular diseases, which is applied in the fields of cardiovascular system diseases, drug combinations, and pharmaceutical formulations, etc.

Inactive Publication Date: 2017-09-12
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the pathogenesis of stroke is different from that of Parkinson's disease, Alzheimer's disease, lateral sclerosis and other diseases, and there is no effective clinical treatment to cure it, the reconstruction and recovery of neurological function is still the key to ischemic brain disease. Challenges in Stroke Treatment

Method used

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  • Application of CDNF (cerebral dopamine neurotrophic factor) in preparation of ischemic cerebrovascular disease drugs
  • Application of CDNF (cerebral dopamine neurotrophic factor) in preparation of ischemic cerebrovascular disease drugs
  • Application of CDNF (cerebral dopamine neurotrophic factor) in preparation of ischemic cerebrovascular disease drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Neuroprotective effect of microinjection of CDNF preconditioning on focal cerebral ischemia-reperfusion in cerebral endocortex

[0032] 1. Intracerebral microinjection and establishment of focal cerebral ischemia-reperfusion model in rats with suture method: the animal experiment process is as follows Figure 1A shown. After Sprague-Dawley rats (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.) were intraperitoneally injected with 10% chloral hydrate, the brains of the rats were fixed on a stereotaxic apparatus, and the skin on the top of the skull was cut to expose the skull. The tip of the herringbone suture on the skull surface is the body surface mark. PBS and 6 μg CDNF were extracted with a micro-sampler and injected into the left cerebral cortex according to the literature method (J Cereb Blood Flow Metab, 1999, 19(12): 1329-1335). After 20 minutes, Make MCAO models.

[0033] SD rats with a body weight of 300±5g were taken,...

Embodiment 2

[0037] Embodiment 2: CDNF is to the neuroprotection of neuron and glial cell in the oxygen glucose deprivation experiment of in vitro culture

[0038] 1. The detection of CCK-8 kit shows the neuroprotective effect of CDNF on neurons cultured in vitro: the neurons cultured in vitro for 7 days were taken to carry out the oxygen-glucose deprivation experiment, and the CCK-8 kit (purchased from Biyuntian Biotechnology Co., Ltd. ) to detect the cell survival rate, the results showed that OGD treatment can reduce the neuron cell survival rate to 64.14 ± 4.09%, and after 50ng / ml CDNF treatment, the cell survival rate can be increased to 72.81 ± 4.97%, after 100ng / ml CDNF treatment, it can The cell survival rate was increased to 80.69 ± 4.21%, and the cell survival rate could be increased to 73.59 ± 5.49% after 100ng / ml NGF treatment ( Figure 3A ), these results show that both CDNF and NGF can increase the cell survival rate of OGD-treated neurons, suggesting that CDNF has neuroprote...

Embodiment 3

[0040] Embodiment 3: the impact of focal cerebral ischemia reperfusion on CDNF expression

[0041] 1. Immunohistochemical method to detect the expression of CDNF in the cerebral cortex of the focal cerebral ischemia-reperfusion model: after 2 hours of ischemia and 24 hours of reperfusion, frozen sections were taken for double immunofluorescence histochemical staining. CDNF-positive cells in the blood-side cortex increased, while the number of NeuN-positive neurons decreased significantly ( Figure 4A ), the number of GFAP-positive astrocytes also increased significantly ( Figure 4B ), some cells are CDNF and NeuN double positive, and some cells are CDNF and GFAP double positive. This suggests that the expression of CDNF is up-regulated in the focal cerebral ischemia-reperfusion cortex, and some NeuN-positive neurons and GFAP-positive astrocytes will secrete CDNF.

[0042] 2. Western Blot detection of the expression of CDNF in the cerebral cortex of the focal cerebral ischem...

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Abstract

The invention relates to the application of the neurotrophic factor conservative dopaminergic neurotrophic factor (cerebral dopamine neurotrophic factor, CDNF) in the preparation of ischemic cerebrovascular disease medicine. The inventors discovered for the first time that CDNF has the function of reducing the area of ​​cortical ischemia and improving the recovery of animal motor ability, and further found that the protective effect of CDNF on neurons and glial cells is not regulated by the endoplasmic reticulum stress pathway. CDNF can be designed as a targeted drug to prevent and treat ischemic stroke, which has great potential application value in the clinical prevention and treatment of ischemic stroke, and lays the foundation for further research on the biological function of CDNF.

Description

technical field [0001] The present invention relates to the application of neurotrophic factor conservative dopaminergic neurotrophic factor (cerebral dopamineneurotrophic factor, CDNF) in the preparation of ischemic cerebrovascular disease drugs, in particular to the application of a new type of neurotrophic factor CDNF in the preparation and prevention of focal cerebral insufficiency The application in blood medicine belongs to the technical field of ischemic stroke medicine. Background technique [0002] Neurotrophic factors (neurotrophic factors, NTFs) are a class of polypeptide or protein factors produced by the body that can promote the survival, growth, and differentiation of nerve cells. Promote neuron repair, axon regeneration, regulate synaptic plasticity and neurotransmitter transmission and other protective functions of the nervous system. Now known neurotrophic factors include: nerve growth factor (nerve growth factor, NGF), brain-derived neurotrophic factor (b...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61P9/10
CPCA61K38/185
Inventor 王晓静张更林赵艳刘挺
Owner SHANDONG UNIV
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