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Use of recombinant adamts13 in the preparation of intracerebral hemorrhage drugs

A technology of uses and drugs, applied in the field of biopharmaceuticals, can solve the problems that have not yet been seen, and achieve the effect of increasing the safety of thrombolysis

Active Publication Date: 2015-07-29
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there is no report on the use of recombinant ADAMTS13 to reduce cerebral hemorrhage caused by tPA thrombolysis after cerebral ischemia

Method used

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  • Use of recombinant adamts13 in the preparation of intracerebral hemorrhage drugs
  • Use of recombinant adamts13 in the preparation of intracerebral hemorrhage drugs
  • Use of recombinant adamts13 in the preparation of intracerebral hemorrhage drugs

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Embodiment 1

[0108] 1. Materials and methods

[0109] (1) Reagents and antibodies

[0110] Evans blue, Drabkin, paraformaldehyde, D-glucose, formamide, wortmannin (purchased from Sigma-Aldrich) (St Louis, MO, USA), human recombinant tPA (Aitone) was purchased from Boehringer Ingelheim (Mannheim, Germany), human VWF protein was purchased from Haematologic Tecnologies (Essex Junction, VT, USA), human recombinant ADAMTS13 was purchased from R&D systems (neapolis, MN, USA), and fasudil was purchased from Calbiochem (San Diego, CA, USA). Primary antibodies include rabbit anti-zonula occludens (ZO-1) (Invitrogen, Camarillo, CA, USA), rabbit anti-collagen IV (Santa Cruz Biotechnology, Santa Cruz, CA, USA), rabbit anti-VEGF (vascular endothelial growth factor) ) (Abcam, MA, USA), goat anti-Angiopoietin(Ang)-1 (Santa Cruz Biotechnology, Santa Cruz, CA, USA), goat anti-Ang-2 (Santa Cruz Biotechnology, Santa Cruz, CA, USA), rabbit anti-phospho-Akt (serine 473) (Cell Signaling Tecnology, Beverly, MA...

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Abstract

The invention belongs to the field of biological pharmacy, relates to application of recombinant ADAMTS13 to preparation of cerebral hemorrhage medicaments, and especially relates to application of recombinant ADAMTS13 to preparation for medicaments for reducing cerebral hemorrhage caused by tPA thrombolytic therapy on cerebral ischemia. Experiment results show that: VEGF generated by tPA induction at ischemic condition can be blocked by a specific inhibitor of RhoA or Akt, and recombinant ADAMTS13 substantially reduces activation of RhoA and phosphorylation of Akt, which means that recombinant ADAMTS1 is capable of inhibiting tPA-induced VEGF expression through RhoA and Akt pathways. The recombinant ADAMTS13 provided by the invention helps to mitigate damage of tPA to blood cerebral barrier and further to reduce cerebral hemorrhage caused thereby by inhibiting cerebrovascular permeability increase mediated by RhoA and Akt, and therefore combination usage of recombinant ADAMTS13 and tPA is a novel countermeasure and means for increasing thrombolysis security.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and relates to the use of recombinant ADAMTS13 in the preparation of cerebral hemorrhage drugs, especially the use of recombinant ADAMTS13 in the preparation of drugs for reducing cerebral hemorrhage caused by tPA thrombolytic therapy after cerebral ischemia. Background technique [0002] Studies have shown that stroke is one of the main causes of human disability and death; and tissue-type plasminogen activator tPA (Tissue Plasminogen Activator) has become the most effective drug for the treatment of stroke due to its powerful thrombolytic effect; However, the use of tPA thrombolysis increases the risk of cerebral hemorrhage. Therefore, how to overcome tPA-induced cerebral hemorrhage is of great significance for reducing the disability and mortality of cerebral apoplexy. [0003] The tPA is a serine protease, which plays an important role in maintaining blood coagulation and fibrinolysis; tPA n...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/48A61P9/10
Inventor 范文英赵冰樵王丽香
Owner FUDAN UNIV
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