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Application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis

A technology of PD149163, 1.PD149163, applied in the field of drug research and development

Active Publication Date: 2017-04-05
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Whether the cooling effect of PD149163 is beneficial to the treatment of stroke and other cerebrovascular diseases has not been reported yet

Method used

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  • Application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis
  • Application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis
  • Application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: Preparation of Focal Cerebral Ischemia-Reperfusion Animal Model

[0030] According to the Longa method, the right middle cerebral artery occlusion (middle cerebral artery) in the monofilament lumen of rats was prepared by using a nylon suture (model: 2634-A4, Beijing Xinong Technology Co., Ltd., China) with the head end coated with polylysine. Arteriocclusion, MCAO) model. SD rats were fasted for 8-10 hours before the operation, anesthetized by intraperitoneal injection of 10% chloral hydrate (0.45ml / 100g, prepared in sterile saline), fixed in the supine position, and made a median neck incision after povidone-iodine disinfection, and separated the right side The common carotid artery, internal carotid artery and external carotid artery were inserted into the clot thread from the incision of the external carotid artery until resistance (approximately 20 mm) appeared, indicating that the clot thread had reached the middle cerebral artery, and the clot thread w...

Embodiment 2

[0031] Example 2: Two-dimensional laser speckle imaging technology

[0032] SD rats were fasted for 8-10 hours before the operation, and the rats were anesthetized with 10% chloral hydrate, and ear sticks were inserted into the ear canals on both sides and fixed on the fixator. After immobilization, the head of the rat cannot move, and the top of the skull is in a horizontal plane. Body temperature The core temperature of the rats was maintained at 36.5°C±1°C by means of an animal body temperature maintenance instrument.

[0033] Use medical scissors to remove the hair from the head of the rat, sterilize with povidone iodine and incise the midline skin (the incision can extend about 1 cm from the line connecting the posterior edges of the eyes), separate the periosteum, sterilize with 3% hydrogen peroxide, and expose the bone. face to determine the position of bregma. Then use a scalpel to carefully grind the skull at the blood flow monitoring area to make it thinner to faci...

Embodiment 3

[0040] Example 3: Experimental grouping, administration and low temperature induction

[0041] SD rats were randomly divided into groups after weighing: sham operation group (Con-Saline), MCAO model group (MCAO-Saline), PD149163 0.5mg / kg group (MCAO-PD149163).

[0042] Administration method: In the experiment of observing the hypothermia effect induced by PD14963, the drug was injected intraperitoneally at 0h, 4h, 7h and 10h after ischemia, and the rectal temperature was monitored every 15min with a rectal probe within 900min after ischemia; to observe the neuroprotective effect of PD149163 In the experiment, the ischemia-reperfusion model animals were given the above drugs by intraperitoneal injection at 1.5h and 4.5h after reperfusion respectively;

[0043] Such as figure 2 As shown, rats were ischemic for 90 min, and PD149163 (0.5 mg / kg) was intraperitoneally injected at 0 h, 4 h, 7 h and 10 h after ischemia, and the effect of PD149163 on rat body temperature was observed...

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PUM

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Abstract

The invention discloses application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis. According to application of PD149163 to preparation of the medicine for treating cerebral arterial thrombosis, on the premise that cerebral blood flow of a focal zone is not affected in the cerebra ischemic reperfusion process, PD149163 plays a protective role in rat cerebral injury at the acute stage caused by focal cerebra ischemic reperfusion. PD149163 possibly resists to nerve cell apoptosis caused at the acute stage of cerebra ischemic reperfusion by blocking an AMPK-mTOR signal channel and inhibiting autophagy.

Description

technical field [0001] The invention belongs to the technical field of drug research and development, and specifically relates to the application of PD149163 in the preparation of drugs for treating ischemic stroke. Background technique [0002] Stroke is a neurological impairment caused by abnormal blood supply to the brain, which can be divided into two categories: ischemic stroke and hemorrhagic stroke. Ischemic stroke is a symptom of localized tissue necrosis and softening caused by cerebral blood supply disturbance, ischemia and hypoxia, which causes focal or complete neurological deficit. Ischemic stroke accounts for about 85% of all stroke cases, and the core mechanism of its injury lies in ischemia, hypoxia and reperfusion injury of brain tissue. At present, more than 5 million people die of stroke every year in the world; in my country, cerebrovascular diseases account for the first cause of death, and with the continuous increase of the elderly population, the num...

Claims

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Application Information

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IPC IPC(8): A61K38/07A61P9/10
CPCA61K38/07
Inventor 孙秀兰季娟曹露露张玲丁旭严辉黄纪烨
Owner NANJING MEDICAL UNIV
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