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Application of dapsone in protection of integrity of blood brain barrier

A technology of blood-brain barrier and dapsone, applied in the field of medicine, can solve the problem that the influence of blood-brain barrier integrity has not been reported yet

Inactive Publication Date: 2014-10-01
崔德华
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The above studies have shown that dapsone can inhibit ROS levels at the cell and animal levels, and reduce the damage caused by oxidative stress, and has a good anti-oxidative stress effect, but the effect of dapsone on the integrity of the blood-brain barrier has not yet been established. to report

Method used

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  • Application of dapsone in protection of integrity of blood brain barrier
  • Application of dapsone in protection of integrity of blood brain barrier
  • Application of dapsone in protection of integrity of blood brain barrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Embodiment 1, animal model construction and treatment.

[0017] Lipopolysaccharide (LPS) stimulation often causes inflammatory changes in blood vessels and nerves, so it is a commonly used inflammation model in the world to explore the effects of drugs on changes in blood vessels and nerves and related pharmacological mechanisms.

[0018] 3-month-old C57 / BL6 mice were selected and raised in the Experimental Animal Department of Peking University Health Science Center, free to forage and drink, and with a 12 / 12h sunshine rhythm. The mice were grouped as follows: solvent group (Control); intraperitoneal injection of LPS group (LPS); intraperitoneal injection of LPS+0.5mg / kg DDS group (LPS+0.5mg / kg DDS); intraperitoneal injection of LPS+2mg / kg DDS group (LPS+2mg / kg DDS); intraperitoneal injection of LPS+5mg / kg DDS group (LPS+5mg / kg DDS); intraperitoneal injection of LPS+20mg / kg DDS group (LPS+20mg / kg DDS), 6 rats in each group. Different concentrations of DDS were dissolv...

Embodiment 2

[0019] Embodiment 2, the impact of dapsone on the BBB leakage caused by LPS

[0020] After the mice were anesthetized with 5% chloral hydrate, a cranial window was opened above the occipital cortex of the skull, and fluorescently labeled MW40,000 dextran was injected into the tail vein, and the integrity of the BBB was checked under a two-photon microscope.

[0021] Implementation results: the BBB of the mice in the Control group was intact, and no fluorescently labeled dextran appeared in the brain parenchyma around the blood vessels; the BBB of the mice in the LPS group leaked, and the macromolecular fluorescent substances in the blood vessels passed through the blood vessels and entered the brain parenchyma; while LPS+5mg / BBB integrity was significantly improved in the kg DDS group compared to the LPS group. The above results show that 5mg / kg DDS administration can reduce the BBB leakage caused by LPS. The two-photon results and the statistical results of the correspondin...

Embodiment 3

[0022] Embodiment 3, the influence of dapsone on the tight junction protein level of mouse brain vessels

[0023] Extract mouse brain microvessels, lyse them with RIPA lysate containing protease inhibitors on ice for 30 minutes, centrifuge to get the supernatant, quantify the protein, perform Western blot analysis, and detect the levels of vascular tight junction proteins ZO-1, Claudin-5 and Occludin .

[0024] Implementation results: Compared with the control group, the level of cerebrovascular tight junction protein in the LPS group decreased significantly, and within 0.5-5mg / kg, with the increase of the concentration of dapsone, the tight junction protein level gradually increased, and at 20mg / kg The time decreased, but there was still a significant difference compared with the LPS group. Compared with control group ##p figure 2 shown.

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Abstract

The invention relates to an application of dapsone (a chemical name is 4,4'-diamino diphenyl sulfone) in protection of integrity of blood brain barrier. The application of a model of blood brain barrier damage caused by lipopolysaccharide inflammatory factors shows that dapsone can be used for reducing the ROS level of a blood vessel of a mouse brain by reducing the activity of DADPH oxidase and the level of DADPH oxidase 2 so as to increase expression of tight junction protein and finally relieving blood brain barrier leakage caused by LPS. The application of the dapsone shows that dapsone can be used for protecting the integrity of the blood brain barrier. The structure preparation of dapsone is as shown in the specification.

Description

technical field [0001] The invention belongs to the field of medicine and relates to the application of dapsone in protecting the integrity of the blood-brain barrier. Background technique [0002] The blood-brain barrier (BBB) ​​is a structure composed of continuous cerebral vascular endothelial cells, which functions to regulate the entry of cells and molecules into the brain and prevent neurotoxic substances from entering the brain from the blood. Tight junction proteins are responsible for maintaining the integrity of the BBB. Dysregulation of the BBB is an early and important event in the pathogenesis of many neurological diseases, thus protecting the integrity of the BBB plays an important role in the treatment of a variety of neurological diseases. [0003] Many in vivo and in vitro stimuli can cause BBB damage, such as lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, which causes increased BBB permeability and decreased tight junction prot...

Claims

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Application Information

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IPC IPC(8): A61K31/145A61P25/00
Inventor 崔德华周婷战锐赵磊王贺成张韬
Owner 崔德华
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