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Effect of Cerebral Ischemia/Reperfusion Injury on Hydroxysafflor Yellow a Penetrating Across the Blood-Brain Barrier

Author: HePingPing
Tutor: FuFengHua;ZhangZuoMei
School: Shandong University
Course: Pharmacology
Keywords: HSYA A Cerebral ischemia and reperfusion Blood-brain barrier Evans Blue High Performance Liquid Chromatography Matrix metalloproteinase-9
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 167
Quote: 1
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Abstract


Objective: ischemic cerebrovascular disease is a common serious harm to human health, disease, thrombolysis and cerebral protection treatment is still the treatment of ischemic cerebrovascular disease two main treatment, Chinese medicine and its active ingredient missing role in the treatment of hemorrhagic cerebrovascular disease is gradually attention. Safflower traditional traditional Chinese medicine mainly used in clinical treatment of ischemic cardiovascular and cerebrovascular diseases. Safflower blood circulation mainly composed of water-soluble safflower yellow. Safflower yellow in the higher levels and active ingredients for HSYA A (hydroxysafflor yellow A, of HSYA), literature, HSYA the anti-platelet aggregation and inhibition of thrombosis, anti-oxidative stress, improve ischemia under the energy metabolism of the brain cells, as well as to reduce the role of glutamate and NaCN-induced neuronal injury. The blood-brain barrier (blood-brain barrier, BBB) is a selective permeability and low permeability material dynamic interface between the blood and the brain parenchyma by the brain capillary endothelial cells (brain capillary endothelialcells, BCECs) tight junctions, basement membrane, pericytes and glial cells foot processes form lack of BCECs contractile proteins, apertures, cell pinocytosis bubble less rich in the enzyme system, this structure determines the macromolecular hydrophilic drugs is difficult to enter the central nervous system, to ensure the stability of the environment within the central nervous system. BBB permeability is not static, cerebral ischemia and reperfusion injury, free radicals and nitric oxide production increased, increased expression of matrix metalloproteinases, inflammatory factors and adhesion molecules, tight junction protein expression was reduced leukocyte aggregation, infiltration, destruction BCECs and basement membrane, resulting in an increase in BBB permeability. Treatment of cerebral ischemia drugs through the BBB, and achieve an effective concentration in the brain tissue in order to play a therapeutic role. Studies have shown that HSYA against cerebral ischemia and HSYA has been approved for the treatment of ischemic cerebrovascular disease clinical trials, But Can HSYA through the BBB HSYA in cerebral ischemia through BBB amount is occurred changes have not been reported. This study cerebral ischemia-reperfusion injury HSYA through the BBB, and to investigate the impact mechanism. Methods: The middle cerebral artery suture prepared by cerebral ischemia 2h 3h or 24h reperfusion injury model. Brain tissue content of Evans blue (EB) quantitative evaluation of BBB permeability changes; reversed-phase high performance liquid chromatographic determination of plasma and brain tissue HSYA content, Coomassie brilliant blue method for the determination of protein in brain homogenates content. The brain tissue HSYA concentration brain tissue HSYA content / protein content (microg / g); enzyme-linked immunosorbent assay in brain homogenates of matrix metalloproteinase -9 (MMP-9) expression. Results: (1) sham-operated rats brain tissue EB content. Sham group, ischemia-reperfusion 3h brain tissue EB content increased significantly, the BBB opening up; ischemia-reperfusion 24h brain tissue EB content increased significantly, the BBB further open. (2) HSYA 10 min after injection, the control group, the brain can be detected of HSYA, reduced to 90 min when the test line. Compared with control group, the sham operation 3H, 24h group of brain tissue HSYA the concentration was no significantly increased; ischemia-reperfusion 3h, the 24h group ischemic brain tissue HSYA the concentrations were significantly increased, not ischemic brain tissue concentrations of HSYA no significant change. (3) sham operation group and sham administration of brain tissue does not detect the expression of MMP-9, compared with the sham group, ischemia reperfusion 3h, 24h brain tissue of MMP-9 expression was significantly increased; with the sham administration group, ischemia-reperfusion 3h, 24h administration brain tissue of MMP-9 expression was significantly increased; ischemia-reperfusion group and ischemia-reperfusion administration brain tissue expression of MMP-9 was no significant different. Conclusion: HSYA through normal the BBB, but the transmission rate is low; cerebral ischemia-reperfusion injury can increase HSYA through the BBB amount, and BBB permeability parallel with the expression of MMP-9 .

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