| bjective:Simulate the evolution of human disease pathop-hysiology explore atorvastatin (atorvastatin, ATO) pretreatment oninterleukin-6(IL-6) and cytokine signal transduction inhibitor-3(SOCS-3)in a large high cholesterol dynamic expression of cerebral ischemia andreperfusion each other, as atorvastatin on hyperlipidemia rat cerebralischemia-reperfusion injury neuroprotective provide an experimentalbasis.Methods:1.a rat model of high cholesterol production: select SDrats95(weighing120~140g), were randomly divided into2groups:normal diet group (n=5), high-fat diet group (n=90) after4weeks,respectively, normal diet group and high-fat diet group rat tail blood,blood tests total cholesterol (TC), triglyceride (TG), low densitylipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol(HDL-C) levels were compared, there is a significant difference (P <0.01),hyperlipidemia rat model was successful;2.The preparation of highcholesterol in rats were randomly divided into90hyperlipidemia modelgroup (HLP, n=15), high cholesterol cerebral ischemia-reperfusion group(HLP/CIR, n=25), low-dose (5mg/kg) ATO preconditioning group (SATO,n=25), high-dose (10mg/kg) ATO preconditioning group (LATO, n=25).Preparation of cerebral ischemia-reperfusion model modified suturemethod is to follow the process, only the corresponding model group operative exposed carotid artery, external carotid artery and carotid artery,but not to plug wire operation. ATO night before surgery pretreated withdifferent doses ATO each vehicle to be gavage once daily for14consecutive days. The same time as the rest of the groups administeredsaline per day.The HLP/CIR, SATO, and LATO3group was divided intothree hours of ischemic reperfusion6h,12h,24h,3d4observation point intime, every subgroup of five rats underwent MRI scans at the appropriatepoint of time, and with saline immediately after cardiac perfusiondecapitated, according to the MRI scan image selection infarct area sliceobserve the corresponding index.At the corresponding time points in eachexperimental group of rats was observed neurological score, wet weightmeasured infarct brain tissue water content, using histopathologicalchanges HE staining brain, ELASA assay IL-6levels, RT-PCR methoddetect the expression of SOCS-3factor.Also in24h after time point wererandomly HLP/CIR, SATO, LATO group of10rats in each group of fivelines after the MRI imaging performed immediately decapitated TTCstaining the location and extent of infarction.The resulting dataapplications SPSS17.0statistical software for statistical analysis. Results:1.Brain lack of high cholesterol in rats after reperfusion, cerebralischemia and reperfusion in the control group (HLP/CIR), a small dose ofatorvastatin intervention group (SATO), high-dose atorvastatin intervene-tion group (LATO) there are different degree of neurological deficit, ipsilateral brain water content increases, appears cell degeneration,necrosis and inflammatory cell infiltration around the ischemic infarctperformance, above all reached the peak at24h, and then graduallydeclined. Magnetic resonance imaging (MRI) imaging and TTC stainingcan clearly show the location and extent of infarction, and consistent.2.Dynamic Interleukin-6(IL-6) and cytokine signal transduction inhibit-tor-3(SOCS-3) expression: high cholesterol in rats after ischemia-reperfusion6h IL-6and SOCS-3factor expression began to increase,with the lipid membrane-type group (HLP) comparison (P<0.05), thedifference was significant, peak appears after perfusion24h, thengradually decreased, remained at a high level after3d.3.high cholesterolin rats after atorvastatin (ATO) pretreatment changes above indicators:①high cholesterol ischemia reperfusion, SATO and LATO2group ofneurological deficit symptoms compared with HLP/CIR group to improvenerve function scores compared with HLP/CIR group was significantlyhigher (P<0.05), SATO and HLP/CIR group6h ischemia-reperfusionwas no significant difference (P>0.05), but reperfusion12h,24h,3d weresignificant differences appeared (P<0.05). LATO group at each time pointand HLP/CIR group were statistically significant (P<0.05).②ATOpretreatment brain water content decrease, compared with HLP/CIRgroup, reperfusion6h, SATO group relative HLP/CIR group was notstatistically significant (P>0.05), reperfusion12h,24h,3d were statistically significant (P<0.05). LATO group relative to the HLP/CIRgroup, each observation time point were statistically significant (P<0.05).③reperfusion24hSATO group and LATO group infarct volumecompared with HLP/CIR group decreased.④with HLP/CIR group, HEstaining showed two ATO pretreatment group were seen at the side of theinfarct cell edema, was "ballooning" nucleus degeneration, pyknoticsmaller or disappear, cell gap widened, surrounding cells and next to thesmall blood vessels visible inflammatory cell infiltration, but the extent ofless than HLP/CIR group, which LATO group cell necrosis andinflammatory cell infiltration were better than SATO group.⑤6h afterischemia-reperfusion to3d, SATO and LATO group content of IL-6inboth the infarct side there was a significant decline, with HLP/CIR groupwere significant differences occurred (P<0.05).⑥After ischemia-reperfusion, SATO and LATO2SOCS-3group compared with HLP/CIRgroup content increased significantly in the infarct, ischemia-reperfusionATO12h to3d two intervention groups with HLP/CIR group developedsignificant difference (P<0.05).Conclusion:1libitum rat model of highcholesterol can fully simulate the evolution of the pathophysiology ofhuman diseases, and on the basis of rat middle cerebral artery occlusionand reperfusion model modified suture method, and human ischemia-reperfusion similar evolution is an excellent model to study drugpretreatment.2high cholesterol in rats after brain ischemia-reperfusion appears: neurological deficits, increased infarction, brain water contentand increased expression of IL-6and SOCS-3factor, and changes in therelationship between these indicators and the correlation between thepresence of aging, indicating missing and brain edema and inflammatorycell infiltration and expression of inflammatory factors related toischemia-reperfusion nerve function.3.ATO pretreated rats with highblood cholesterol in brain ischemia-reperfusion injury could inhibit theexpression of inflammatory cytokines IL-6, and raised factor SOCS-3expression, cerebral edema, reduce inflammatory cell infiltration, reducedinfarct volume, the brain has a protective effect.4.ATO high cholesterolin brain ischemia-reperfusion injury in rat neural protective effect anddose-effect relationship exists, large doses than small doses. |
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