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Effects Of The Rats NMDARmRNA Expression In Brain Zones Induced By Sub-chronically Benzo"a"pyrene And The Neuroprotective Effect Induced By Geranylgeranylacetone

Posted on:2012-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:S S ChangFull Text:PDF
GTID:2154330332996464Subject:Health Toxicology
Abstract/Summary:PDF Full Text Request
Objective:Observation of effects of sub-chronically benzo[a]pyrene on rat neurobehaviour,detect the expression ofNMDARmRNA in different zones.Ivestigate benzo[a]pyrene neurotoxicity and its mechanism ofneurotoxicity.Methods:Fifty male SD rats,adult and healthy,were randomly divided into 5 groups:blank control,olive control,1.0,2.5,6.25mg/kg B[a]P groups.After exposure by benzo[a]pyrene intraperitioneal injection,90day.TheMorris water maze test was perfomed to test the learning and memory abilities of rat. Light and electricmicroscopic were used to observe the morphological changes in rat's hippocampus induced bybenzo[a]Pyrene;Detect NMDAR1,NMDAR2A,NMDAR2BmRNA expression in different rat brain zones byQRT-PCR.,conclude,hippocampus,cerebral cortex,cerebellum and corpus.Results:Intraperitoneal rat subchronic exposure B[a]P experiment:The rat's body weights all grew,The weight ofrats in all groups,the growth rate is less than the control and solvent control group.When the exposureended,The B[a]P2.5,6.25mg/kg group's results are statistically significant compared with the controlgroup,the solvent control group and B[a]P1.0mg/kg group(P<0.05).The Morris water maze test showed, 2.5mg/kg B[a]P group's escape latencies of navigationtest is significantly lower than the control group's,compared with 1.0mg/kg B[a]P group's the differencesare statistically significant(P<0.05).6.25mg/kg B[a]P group's escape latencies of navigation test wassignificantly higher than the control group's,the solvent control group's and 1.0 mg/kg B[a]Pgroup's(P<0.05).and 2.5,6.25mg/kg B[a]P group's total road of navigation test was significantlyhigher than the control group's,the solvent control group's and 1.0 mg/kg B[a]Pgroup's(P<0.05). the solvent control group's(0.45). And 6.25mg/kg B[a]P group's durations of the thirdquadrant are lower than the other group's,the differences are statistically significant(P<0.05).By immunohistochemistry,we found that,compared with the other groups,the Neural cell apoptosis inB[a]P6.25mg/kg group was significantly decreased and the difference was significant (P<0.05).The expression of different zones'NMDAR1,NMDAR2A,NMDAR2BmRNA was detected usingQuantitive real time PCR.Compared with the other groups,the expression in 6.25mg/kg B[a]P group was significantly decreased and the difference was significant(P<0.05),in the four gene expression.Correlation analysis showed that there have a correlation between the early apoptosis rate and theexpression of the Hsp70 protein and the Hsp70,NMDAR1,NMDAR2A,NMDAR2BmRNA,and thecorrelation coefficient r=-0.886,-0.921,-0.955,-0.890,-0.936(P<0.05).Conclusion:Subchronic exposure to benzo[a]pyrene can lead to rats learning and memory damage. Sub-chronicexposure to benzo[a]pyrene in rat hippocampus induced hippocampus pathological changes,and theexpression of NMDAR1,NMDAR2A,NMDAR2BmRNA decreased may be related with benzo[a]pyreneneurotoxicity.Partâ…¡Objective:To study the GGA neuroprotective effect on the rats by sub-chronically benzo[a]pyrene .Methods:Forty male SD rats,adult and healthy,were randomly divided into 4 groups:olive control, GGA+ olivecontrol,GGA+6.25mg/kg and 6.25mg/kg B[a]P groups.GGA was given orally with a dose (800mg/kg) to therats in GGA group and exposure by benzo[a]pyrene intraperitioneal injection,90day.The Morris water mazetest was perfomed to test the learning and memory abilities of rat. Light microscopic were used to observethe morphological changes in rat's hippocampus induced by benzo[a]Pyrene;DetectHsp70,NMDAR1,NMDAR2A,NMDAR2BmRNA expression in different brain zones(hippocampus,cerebralcortex,cerebellum and corpus) by QRT-PCR..Results:Intraperitoneal rat subchronic exposure B[a]P experiment:The rat's body weights all grew. The6.25mg/kg B[a]P group's results are significant lower than the solvent control group ,the GGA+ solventcontrol group and the GGA+ 6.25mg/kg B[a]P group(P<0.05).The Morris water maze test showed, 2.5mg/kg B[a]P group's escape latencies of navigationtest is significantly lower than the control group's,compared with 1.0mg/kg B[a]P group's the differencesare statistically significant(P<0.05).6.25mg/kg B[a]P group's escape latencies of navigation test wassignificantly higher than the control group's,the solvent control group's and 1.0 mg/kg B[a]Pgroup's(P<0.05).and 2.5,6.25mg/kg B[a]P group's total road of navigation test was significantlyhigher than the control group's,the solvent control group's and 1.0 mg/kg B[a]Pgroup's(P<0.05). the solvent control group's(0.45). And 6.25mg/kg B[a]P group's durations of the thirdquadrant are lower than the other group's,the differences are statistically significant(P<0.05).By immunohistochemistry,we found that,compared with the other groups,the Neural cell apoptosis in B[a]P6.25mg/kg group was significantly decreased and the difference was significant (P<0.05).The expression of different zones'NMDAR1,NMDAR2A,NMDAR2BmRNA was detected usingQuantitive real time PCR.Compared with the other groups,the expression in 6.25mg/kg B[a]P group wassignificantly decreased and the difference was significant(P<0.05),in the four gene expression..Conclusion:Subchronic exposure to benzo[a]pyrene can lead to rats learning and memory damage. Sub-chronicexposure to benzo[a]pyrene in rat hippocampus induced hippocampus pathological changes,and theexpression of NMDAR1,NMDAR2A,NMDAR2BmRNA decreased may be related with benzo[a]pyreneneurotoxicity.
Keywords/Search Tags:B[a]P, Learning and memory, Hsp70, Hippocampus, GGA
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