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Relation Between The Enzyme Activity And Gene Mutation Of Platelet-activating Factor-acetylhydrolase Ⅱ And Cerebral Thrombosis

Posted on:2006-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:B L ChenFull Text:PDF
GTID:2144360152492663Subject:Neural Molecular Biology
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Cerebral thrombosis has high morbidity and disability rate.There are still no definite conclusions about its happenning mechanism.Now it is wildly accepted that many active media and several gene mutations relate to cerebral thrombosis. So it is necessary to search for more candidate gene mutations and make out their relations to cerebral thrombosis.Experiments have tested that platelet-activating factor takes part in a series of pathophysiology reactions of cerebral thrombosis. Platelet-activating factor-acetylhydrolase hydrolyze the sn-2 acyl groups of platelet-activating factor,which makes the later inactive. The decrease of activation of platelet-activating factor-acetylhydrolase in body results in cerebral thrombosis indirectly. Platelet-activating factor-acetylhydrolase has two forms: plasmic and cytotype.Studys infor that the Val279Phe mutation in the 9th exon of plasma platelet-activating factor-acetylhydrolase is one of independent dangerous factors of cerebral thrombosis. Platelet-activating factor-acetylhydrolase II has homoioplastic sequence and same substrate specificity with plasma platelet-activating factor-acetylhydrolase.Also experiments have confirmed that platelet-activating factor-acetylhydrolase II can inhibit the reactions of oxidat stress and the aggregation of inflammatory cells.There areneither study about the enzyme activity of platelet-activating factor-acetylhydrolase II nor reports on its gene mutations.This study detects the activity of platelet-activating factor-acetylhydrolase II of cerebral thrombosis group and control group using PAF acetylhydrolase assay kit brought from Cayman company,in order to make out if the enzyme activity changes after cerebral thrombosis takes place.From the result we can see the relation between the enzyme activity and cerebral thrombosis.We also amplify the 7th ,the 8th,the 9th and the 10th exons which are around the active center of the enzyme with PCR and dectect if there is mutation in these exons with DHPLC.From the experiment we can see:l.The enzyme activity of those who get cerebral thrombosis no longer then 7 days is notably higher than it of control group and the enzyme activity increases remarkably in serious cerebral thrombosis patients.These findings demonstrate that the activity of platelet-activating factor-acetylhydrolase II works against PAF and protects brain cells during the acute stage of cerebral thrombosis.2.There is Thr241Ser mutation in the 8th exon of platelet-activating factor-acetylhydrolase II. The location of this mutation is very similar to Val279Phe in the 9th exon of plasma platelet-activating factor-acetylhydrolase. This mutation has not been reported before and the enzyme activity of the patient who has this mutation decreases markedly. But the mutation is so seldom that we don't think it has relation to cerebral thrombosis.3.We have not found any mutation in the7th,the 9th and the 10th exon of platelet-activating factor-acetylhydrolase II.
Keywords/Search Tags:Platelet-activating Factor-acetylhydrolase II, Cerebral Thrombosis, Enzyme Activity, Gene
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