| At present, the main methods to cure ischemic stroke include dissolving thrombus, anticoagulantion and dilution to recover the blood-supply, increase blood perfusion in brain. But literatures showed that recovering the blood-supply in brain tissue during some period can aggravate the damage for brain because of oxygen-supply. This results from lots of reactive oxygen species (ROS) generated from ischemia/reperfusion in brain and lipid peroxidation initiating by ROS,generating lots of free radicals, resulting in the decrease of membrane fluidity, the increase of membrane permeation, the swelling of mitochondria and damage of lysosome, and then the irreversible damage of brain cells. Thus, the scavengers for free radicals were considered to use in clinic as soon as possible to cure ischemic stroke. The antioxidants can scavenge free radicals, decrease the contents of hydroperoxide and increase the antioxidative effect of cells, and they can increase the use ratio of oxygen and glucose in ischemic tissues, inhibit the unbalance of electrolyte, and increase the viability of cells. Thus, the antioxidants can retard the development of physiopathologic process from ischemia and inhibit the tardy necrocytosis from reperfusion, and then recover the cells in reversible state.The primary enzymatic defenses in organism are superoxide dismutase (SOD), which catalyses the conversion of superoxide radicals (O2?-) into H202, plus catalase (CAT) and glutathione peroxidase (GPX), both of which destroy H202. Among these enzymes, GPX plays an important role. Due to the limitations associated with native GPX (large molecular weight, instability in vivo and limited availability, short half lives, difficulty in expressing by genetic engineering.), scientists have made a great deal of efforts to study the GPX mimics and the biologic effects of GPX mimics. The well-known GPX mimic, Ebselen, has been undergoing in Ⅲ phase clinic trial as antioxidant in Japan, but its GPX activity is only 0.99U/ (mol. Since the end of 1980's, we have successfully synthesized a series of GPX mimics with high GPX-like activities using the chemical and biologic methods according to the relation between the structure and function of native GPX. Among these mimics, the activity of 2-SeCD is 7.4 U/(mol and its activity is 7.5 fold as much as that of ebselen. We have analyzed its structure by using elemental analysis, IR, 1H NMR, 13C NMR and X-ray photoelectron spectroscopy. The large-scale preparation of 2-SeCD has been investigated by using HPLC. The antioxidaive effects of 2-SeCD has been demonstrated in the level of organella(mitochondria)and the level of cell(cultured rat epidermal cell, NIH3T3 fibroblast and keratinocytes). We found that the antioxidaive ability of 2-SeCD is stronger than that of ebselen, thus, 2-SeCD has potential perspective for pharmacological applications. 1. Effects of 2-SeCD on Stroke in Stroke-Prone Spontaneously Hypertensive RatsIn order to investigate the effect of 2-SeCD on stroke, we observed the effect of 2-SeCD on systolic blood pressure (SBP), heart rate, survival time of rats, clinical score of stroke and the pathomorphology of their brain and carotid artery in stroke-prone spontaneously hypertensive rats (SHRsp)。Results showed that 2-SeCD has strong antioxidative effect and it can be used to cure stroke. The determination of SBP and heart rate showed that 2-SeCD can remit the symptom by decrease the SBP and heart rate. By comparing the survival time of rats, we can draw an conclusion that 2-SeCD can prolong the survival time of SHRsp, indicating that 2-SeCD can retard the development of stroke. Clinical score of stroke of SHRsp administrated 2-SeCD for two weeks decreased greatly, indicating that 2-SeCD can be used to treat stroke. Electron microscope study showed that the endothelium cells of carotid artery and brain cells of SHRsp administrated 2-SeCD were only slightly damaged compared with control group, indicating that 2-SeCD may effectively protect the endothelium cells of carotid artery and...
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