| The Polysaccharide sulfate (PSS) is a new type heparinoid, extracted from phylumphaeophyta. After esterification and sulfonation, the PSS was obtained as a semi-synthetic oceanic drug. The studies on the animal and human showed that PSS could improve microcirculation and coronary blood supply, inhibit blood coagulation, and was effective in the treatment of ischemic heart or brain disease. The recent studies indicated that PSS could block calcium channels and attenuate cultured neurons apoptosis. However, it is not reported that the protective effects of PSS on cerebral ischemia-reperfusion (I/R) injury.The rat model of focal cerebral ischemia-reperfusion was established with the middle cerebral artery occlusion (MCAO) by reversible inserting a nylon thread method. In this study, one-hundred-eighty healthy SD rats (280~320g) were randomly divided into six groups. Namely, sham operation group; cerebral ischemia-reperfusion group; Nimodipine(Nim) O^mg-kg"1 group; three dose groups of PSS (13.5,18,24mg-kg-1, respectively) .The drugs were administered by intraperitoneally (ip) before established MCAO fourty minutes. Rats were killed after ischemia 1 hour and reperfusion 2 hours. Brain were fetched out and measured the contents of [Ca2+]i ,Na+, K+, H2O, NO, MDA and the activities of SOD and NOS. The sections were stained with hemotoxylin-eosin (HE), histological changes of brains were also observed in other six rats.Results: 1 .The effects of PSS on Na+, K+, H2O contents in the brain.1.1. Compared with sham operation group, Na+, H2O contents were highersignificantly but K+ contents were lower significantly in cerebral ischemia-reperfusion group (P<0.01).1.2. Compared with I-R group, Na+, H2O contents were lower significantly but K+ contents were higher significantly in PSS 13.5,18,24mg-kg-1 and Nim0.2mg-kg-12. The effects of PSS on [Ca2+]s contents in the cortex of brain.2.1 Compared with sham operation group, [Ca24]i contents were higher significantly in I-Rgroup(p<0.01).2.2 Compared with I-R group, [Ca2+]i contents were lower significantly in PSS13.5,18 ,24 mg-kg"1 and Nim 0.2 mg-kg"1 groups(p<0.01).3. The effects of PSS on activity of SOD and MDA content in the brain.3.1. Compared with sham operation group, the activity of SOD was significantly lower but MDA contents were significantly higher in I-R group (PO.01).3.2. Compared with I-R group, the activity of SOD was increased significantly, but MDA contents were decreased significantly in PSS 13.5,18,24mg-kg"1 groups and Nim 0.2 mg-kg'1 group (PO.01).4. The effects of PSS on activity of NOS and NO content in the brain.4.1. Compared with sham operation group, the activity of NOS and NO contents were increased significantly hi I-R group (PO.01).4.2. Compared with I-R group, the activity of NOS and NO contents were decreased significantly in PSS 13.5,18,24mg-kg"1 groups and Nim 0.2 mg-kg"1 group (PO.01).5.The effects of PSS on the pathological change in the brain.Pathological findings showed that there were cerebral edema widely, neuronal cells necrosis and partial formation malacoma focal in the model group. The findings also showed that PSS(13.5,18,24 mg-kg"1) were able to relieve brain edema and neuronal cells necrosis, malacoma focal was disappeared. Conclusion:1. This study demonstrates that PSS has protective effects on cerebral ischemina-reperfhsion lesion.2. The possible protective mechanism of PSS might be associated with increasing K+and decreasing Na+, [Ca2+]i, H2O, NO, MDA contents increasing activity of SOD anddecreasing activity of NOS. |
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