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Protective Effect And Mechanism Study Of The Extractive Of Gleditsia Sinensis Lam (GSL) To The Rats During Acute Cerebral Ischemia-Reperfusion Injury

Posted on:2008-11-24Degree:MasterType:Thesis
Country:ChinaCandidate:K H FanFull Text:PDF
GTID:2144360218960037Subject:Pharmacology
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OBJECTIVE:In the experiment, we established the model of acute cerebral ischemia reperfusion (I/R) in rats to observe the effects on nerves function damages,cerebral infarction volume,malondialdehyde (MDA) content in serum,myeloperoxidase (MPO) and nitric oxide (NO) content in brain tissue,tumor necrosis factor-[alpha] (TNF-α)and nuclear factorκappaB (NF-κB) expressed in brain, after administering the different dosages of extractive of Gleditsia sinensis Lam (GSL) by mouth. We estimated the possible protect mechanism of extractive of GSL to the rats during cerebral ischemia reperfusion injury, and the possibility of GSL to cure cerebral ischemia disease in clinic.METHODS: We established the model of acute focal cerebral I/R by middle cerebral artery occlusion (MCAO) with clew. 72 SD male rats were randomly divided into 6 groups: sham-operation group, cerebral I/R model group (negative control), complex Salvia Miltiorrhiza group (positive control, 32 mg/kg·d-1), extractive of GSL groups (150mg/kg·d-1, 75mg/kg·d-1 and 38mg/kg·d-1). Medication groups were successive administered 3 days before operation, and then built the cerebral I/R models, however rats in sham-operation group were only sew up the skin after exposing the common carotid artery (CCA),external carotid artery (ECA), internal carotid artery (ICA) in the right side. After 2 hours of MCAO, we pulled out the clew to recovery the cerebral blood supply. And after 24 hours of reperfusion, neurological deficit were scored, cerebral histomorphology was observed by light microscope; and the cerebral infarction volume was measured by 2,3,5-triphenytetrazolium chloride (TTC) staining technique; NO,MPO,MDA,TNF-αNF-κB levels were detected by chemical and immuno-histochemical methods.RESULTS: We established cerebral I/R model successfully in rats by MACO, and the rats in model group appeared obviously ethology changes after 24 hours of cerebral I/R, then cerebral histomorphology changed, NO production increased, inflammatory reaction and lipid peroxidation were actived. Compared with I/R model group, scores of neurological deficit and infarct volume were significantly lower in the groups treated with extractive of GSL and complex Salvia Miltiorrhiza (p<0.01,p<0.05), and the NO,MPO,MDA,TNF-α,NF-κB levels were also found decreased in all of GSL and complex Salvia Miltiorrhiza groups (p<0.01, p<0.05).CONCLUSION: The extractive of GSL could improve nerves function and diminish cerebral infarction volume after acute cerebral ischemia reperfusion in rats, and the possible mechanism seemed to be that it could release the injury of lipid peroxidation, reduce production of NO and inhibit the inflammatory reaction.
Keywords/Search Tags:Cerebral ischemia reperfusion, Gleditsia sinensis Lam(GSL), nitric oxide (NO), lipid peroxidation, inflammatory reaction
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