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Application of growth differentiation factor 11 in preparation of medicine for treating ischemic stroke

An ischemic stroke, growth differentiation factor technology, applied in cardiovascular system diseases, drug combinations, medical preparations containing active ingredients, etc. Defect score, the effect of promoting cell proliferation in brain region

Inactive Publication Date: 2018-01-16
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because many drugs have problems such as weak efficacy and many side effects, it is still a long way to go to find efficient and safe therapeutic drugs

Method used

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  • Application of growth differentiation factor 11 in preparation of medicine for treating ischemic stroke
  • Application of growth differentiation factor 11 in preparation of medicine for treating ischemic stroke
  • Application of growth differentiation factor 11 in preparation of medicine for treating ischemic stroke

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Therapeutic effect of GDF11 exogenous recombinant protein in cerebral ischemic injury after ischemia

[0046] 1. Establishment of focal cerebral ischemia-reperfusion model in rats with suture method (Middle cerebral arteryocclusion, MCAO model):

[0047] Sprague-Dawley rats with a body weight of 300±5g (purchased from Beijing Weitong Lihua Company) were taken, and after intraperitoneal injection of 10% chloral hydrate (0.3-0.4ml / 100g body weight), they were fixed on the operating table in supine position, and A midline incision was made, the subcutaneous tissue was bluntly dissected, the left common carotid artery (CCA) was dissected and ligated, and the bifurcation of the internal carotid artery (ICA) and external carotid artery (ECA) was dissected upward along the CCA, and the proximal end of the ECA was ligated. Cut a small opening at the intersection of the common carotid artery, and insert a 0.25mm-diameter tethered suture into the ICA at about 20.5±0.5m...

Embodiment 2

[0062] Example 2: The preventive effect of overexpression GDF11 preconditioning in cerebral ischemic injury

[0063] 1. Detection of GDF11 overexpression virus efficiency:

[0064] In order to establish a state of long-term high expression of GDF11 in the brain and study its preventive effect on cerebral ischemic injury, the inventors first constructed a GDF11 overexpression plasmid packaged into a lentivirus with green fluorescent protein (GFP), and The overexpression efficiency of the virus was detected by in vivo and in vitro experiments. 293 cells were recovered and cultured, and when the cell density reached about 80%, 5 μg of negative control virus and GDF11 overexpression virus were added respectively, and fluorescence real-time quantitative PCR was performed 48 hours later. The results showed that the mRNA level of GDF11 overexpression virus was higher than that of the blank virus group 6 times (control group: 1±0; GDF11 overexpression group: 6.08±0.14). The inventor...

Embodiment 3

[0075] Example 3: The molecular mechanism of GDF11 in the treatment and prevention of cerebral ischemic injury

[0076] The cortical ischemic penumbra tissues of cerebral ischemic animals were collected separately, and the protein was extracted for Western Blot. The results showed that after injection of exogenous recombinant GDF11 protein, pSmad2 / 3 in the brain (control group: 1±0.09; GDF11 protein group: 2.0± 0.24; Figure 14 A and B) significantly increased expression. It can be seen from the results that the recombinant GDF11 protein participates in the treatment process of cerebral ischemic injury by regulating Smad2 / 3.

[0077] The tissue protein in the ischemic penumbra of the cortex was extracted and detected by Western Blot. It was found that after injection of the GDF11 overexpression virus, pSmad2 / 3 in the rat brain (control group: 1±0.66; GDF11 overexpression group: 1.57±0.10; Figure 14 The amounts of A and C) are significantly increased. It can be seen from th...

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Abstract

The invention relates to application of growth differentiation factor 11 in the preparation of a medicine for treating ischemic stroke. In the rat model of focal cerebral ischemia reperfusion caused by middle cerebral artery occlusion, treatment and prevention effect of the growth differentiation factor (GDF11) on cerebral ischemic injury is researched. It is found that the GDF11 has functions ofreducing cortical ischemia volume and improving and recovering animal exercise capacity, and furthermore it is found that the GDF11 has a mechanism of action in treating and preventing cerebral ischemic injury and the process is realized by activating a Smad2 / 3 signal channel. The GDF11 can be designed as a targeted drug to prevent and treat ischemic stroke. The invention has latent huge application value for clinical prevention and treatment of ischemic stroke and lays a foundation for further research on biological function of the GDF11.

Description

technical field [0001] The invention relates to the application of growth differentiation factor 11 (Growth differentiation factor 11, GDF11) in the preparation of drugs for ischemic cerebral apoplexy, and belongs to the technical field of ischemic cerebral apoplexy drugs. Background technique [0002] Stroke is one of the common diseases in clinical practice. It has the characteristics of high morbidity, mortality and disability. There are two causes of stroke. %; the other is ischemic stroke caused by intracerebral ischemia and hypoxia due to thrombosis blocking cerebral arteries, accounting for 80%. After focal cerebral ischemia, the blood flow in the ischemic core area drops sharply, and a large number of neurons die. The tissue necrosis in this area is irreversible. But the region bordering the ischemic core, called the ischemic penumbra, was considered a potentially salvageable area. At present, there are three types of drugs commonly used in the treatment of ischemi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P9/10
Inventor 王晓静赵艳王莉红刘挺
Owner SHANDONG UNIV
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