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Protective Effects Of Astragaloside â…£ On Cerebral Ischemia/reperfusion Injury And Expression Of APE-Ref-1 In Rats

Posted on:2006-03-23Degree:MasterType:Thesis
Country:ChinaCandidate:J J YanFull Text:PDF
GTID:2144360155459451Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Ischemic cerebral vascular diseases (ICVD) were principle diseases result in loss of motor ability, linguistic functionN cognization with higher mortality. Although the thrombolytic therapy of ICVD commonly used in clinical led to recanalize of obstructed cerebral vessels, it caused more severe functional and structural damage of brain tissue. It was very important to study the pathophysiological mechanisms of ICVD, to develop effective drugs and explpre possible drug targets of ICVD.Drugs against oxygen free radicals (OFR) may be used in the treatment of I/R injury of brain tissue due to there were harmful effects of OFR. Astragalus, a kind of traditional Chinese medicine had been used in stroke for many years. It was thought that this application was concerned with its effects against OFR. Astraloside, active fractions of astragalus were OFR scavenger. Among the astragalosides, astragaloside IV (AST) was one of active fraction with the highest content, better water solubility and activity. It was expected to be developed a new drug against I/R injury of brain tissue.Adult Wistar male rats were divided randomly into 4 groups, namely, the sham group (Sham), the modle group (M), the drug treated groups (AST 1 and AST 2 group). AST (1 mg/kg and 4 mg/kg) were given to rats in AST 1 and AST 2 groups by intraperitoneal injection before 0.5 h ischemia, while thesame volume of normal saline was given to rats in Sham and M. All groups except sham were subjected to unilateral middle cerebral artery occlusion (MCAO) via insertion of a suture into the left cerebral artery. Blood flow was restricted to the left side of the brain for 1 h, at which time the suture was withdrawed and the animals was allowed to survive for 6 h. The symptoms of neurological defect, the score of behavior, the size of infarction and the pathomorphological changes of rats in each group was observed.In M, the injury of brain tissue was severe. Rats showed marked symptoms of neurological defect with higher score of behavior (7.80±1.03); larger size of infarction (20.23±5.81 %) and obvious pathomorpholoical changes. HE stain slides showed that the space of the hippocampal CA1 pyramidal cells enlarged and there was appearance of edema around the cells. But the morphous of cells is normal on the whole.Compared with that of M, the symptoms of neurological defect were improved and score of behavior marked decreased (7.80±1.03 vs 4.10±0.99^ 6.20±1.63, P<0.01) in AST 1 and AST 2. Size of infarction reduced significantly (20.23±5.81% vs 7.38±2.07% > 16.10*4.15% , P<0.0l). Pathomorphological changes showed that space of the hippocampal CA1 pyramidal cells diminished and edema around the cells alleviated.Compared AST 2 to AST 1, the score of behavior (6.20±1.63 vs 4.1Q±0.99, P<0.0l) and size of infarction (16.10±4.15% vs 7.38±2.07%, PO.01) was highly decreased. The dose of 4 mg/kg of AST 2 is more effective in treating cerebral I/R than that of 1 mg/kg.In order to investigate the mechanism of AST, activity of SOD and content of MDA in hippocampus were observed. Compared with that of Sham, the activity of SOD was decreased significantly (59.88±8.20 vs 43.10±7.40...
Keywords/Search Tags:apurinic/apyrimidinic, endonuclease/redox-factor 1, astragaloside â…£, cerebral ischemia/reperfusion injury, oxygen free radicals
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