Effects Of Atorvastatin Pretreatment On Cerebral Edema And Aquaporin4 Expression In Rats With Focal Cerebral Ischemia

ObjectiveTo investigate the effects of atorvastatin pretreatment on cerebral edema and AQP4 expression in rats with focal cerebral ischemia and explore the possible mechanism of atorvastatin to ischemic brain edema.Methods51 adult male Sprague-Dawley rats were randomly divided into 3 groups:sham-operated(Sham)group,cerebral ischemia(MCAO)group and atorvastatin treatment(Ator)group.Ator group was administered atorvastatin 20mg/kg once for 7days by gavage before operation,while the other groups were administered the same volume of saline matching.Except Sham group,MCAO group and Ator group were subjected to permanent middle cerebral artery occlusion using modified intraluminal suture method.24 hours after operation modified neurological severity scores(m NSS)were checked in 3 groups with a 18-point scale,infarct volume were verified by 2%triphenyltetrazolium chloride(TTC)staining,brain water content(BWC)was determined by wet-dry weight ratios.Expression levels of phosphorylated-p38MAPK(p-p38MAPK)and AQP4 in peri-infarction were checked with immunohistochemistry and Western blot,and m RNA levels of p38 MAPK and AQP4 were checked with quantitative Real-Time polymerase chain reaction.Results(1)Behavioral score: The m NSS of MCAO group(11.00 ± 1.90)was increased compared with Sham group(0),the difference was significant(P<0.001).Ator group m NSS(8.76 ± 1.60)was decreased compared with MCAO group,there was significant difference in both groups(P< 0.001).(2)Cerebral infarct volume: Brain slices of Sham group were evenly red by TTC staining.The ischemic cerebral slices of MCAO group showed a large area infarction and the infarct volume was 23.84%,while the infarct volume of Ator group(13.26%)significantly reduced compared with MCAO group.(3)Brain water content: the ipsilateral BWC of MCAO group(83.85 ± 1.44)was higher than that of Sham group(78.47 ± 1.47)and the difference was significant(P<0.001).Ator group BWC(81.14 ± 1.28)was reduction compared with MCAO group,the difference was statistically significant(P=0.017).(4)m RNA levels: The m RNA levels of p38 MAPK and AQP4 in peri-infarction in MCAO group were prominently up-regulated,and the difference was statistically significant(P< 0.01)compared with Sham group.While the m RNA levels of the both were down-regulated in Ator group(P< 0.05).(5)Cells and protein expression: In MCAO group,positive cells and protein expression of p-p38 MAPK and AQP4 in peri-infarction were significantly higher than Sham group(P<0.01).In Ator group,the cells and protein expression of the both were significantly decreased compared with MCAO group(P< 0.05).Conclusion(1)The m NSS and BWC of ipsilateral brain tissues were significantly increased after cerebral ischemia.The m RNA levels of p38 MAPK and AQP4 in peri-infarction were prominently up-regulated,and positive cells and protein expression of p-p38 MAPK and AQP4 were significantly increased.(2)Atorvastatin could dramatically decreased the BWC of ischemic hemisphere.The m RNA levels of p38 MAPK and AQP4 in peri-infarction were down-regulated,and the expression of p-p38 MAPK and AQP4 were also reduction.While neurological deficits were dramatically improved.(3)The mechanism of atorvastatin alleviating ischemic cerebral edema may decrease expression of AQP4 through a p38MAPK-suppression pathway.