| Objective:To investigate the effects of the limb repeated transient ischemic preconditioning on the expression of IL-6,JAK2 and STAT3 after focal cerebral ischemia/reperfusion in rats with hyperlipidemia.Repeated transient limb ischemic preconditioning on ischemia reperfusion injury of JAK2/STAT3 signal transduction pathway,and limb ischemic preconditioning treatment of cerebral protective effect and the possible mechanism.Methods:Establishment of hyperlipidemia rats model:100 SD rats by using random number table were randomly divided into 2 groups:normal diet group 10,free feeding with normal diet,high fat diet group was 90,with free high fat diet feeding.The modeling time is 4 weeks.After the model was completed,fasting 10h was taken,and the tip of the tail vein blood was taken.The venous blood centrifugation,using automatic biochemical analyzer detect rats serum lipid indexes:total cholesterol(TC),triglyceride(TG),high density cholesterol(HDL-C),low density cholesterol(LDL-C),blood lipid indexes were compared between the two groups.The successful model of 90 hyperlipidemia rats were randomly divided into 3 groups:sham operation group(30 rats),cerebral ischemia reperfusion group(30 rats),limb ischemic preconditioning group(30).Sham operation group:rats after anesthesia,the right common carotid artery,internal carotid artery,external carotid artery were exposed and separated,but the middle cerebral artery was not inserted into the bolt line to keep the blood flowing,and then suture.Cerebral ischemia reperfusion group:suture method according to Longa making middle cerebral artery ischemia reperfusion(MCAO)model of right middle cerebral artery occlusion in rats 2h after reperfusion.The limb ischemic preconditioning group:middle cerebral artery occlusion was performed immediately after the preparation of LIP model preparation,give rats middle cerebral artery occlusion reperfusion after 2 hours.The model group after reperfusion for 6h,12h,24h,48h,72h 5 time points divided into 5 subgroups,5 rats in each sub group.At the 5 corresponding time points,the scores of nervous functional defects were carried,water content of brain tissue were detected by the dry-wet weight method,brain tissue pathological changes were observed by HE stain,dynamic expression of IL-6,JAK2 and STAT3 were observed by immunohistochemical method in rats of differen groups?In addition,each group of 24h reperfusion time point,additional 5 rats were stained with TTC staining method to measure the volume of cerebral infarction.Results:1.The total cholesterol,high fat diet group,triglyceride,low density lipoprotein cholesterol was significantly higher than the normal diet group(P<0.01).2.At each time point,the sham operation group did not appear obvious nerve function injury;Cerebral ischemia reperfusion model group and limb ischemic preconditioning group were all with varying degrees of neurological deficits,but at the corresponding time point,the score of the limb ischemic preconditioning group rats nerve injury was significantly lower than that in the cerebral ischemia reperfusion model group(P<0.01).3.TTC staining and the volume of cerebral infarction:Sham operation group hyperlipidemia rats brain tissue TTC staining showed uniform red,normal color,shape is regular,not observed swelling and pale,it showed sham operation group had not appear at the time of reperfusion after cerebral infarction 24h.Cerebral ischemia reperfusion model group and ischemia preconditioning group in cerebral ischemia reperfusion after 24h of brain tissue can clearly observe the boundary is clear,the color is pale,the size of the cerebral ischemic infarction.24h in cerebral ischemia reperfusion,the cerebral infarct volume of cerebral ischemia reperfusion group rats was significantly higher than that in sham operation group(P<0.01);ischemic preconditioning group rats cerebral infarction was significantly lower than that of the cerebral ischemia reperfusion model group(P<0.01).4.At each time point,the sham operation group rats brain tissue water content had no obvious increase;the brain tissue of cerebral ischemia reperfusion rats in the model group water content were significantly higher than sham operation group(P<0.01);limb ischemic preconditioning rats group the fabric of moisture content was significantly lower than that of the cerebral ischemia reperfusion model group(P<0.05).5.Irrigation time is 6h,12h,24h,48h,72h,cerebral ischemia-reperfusion injury model group rats interleukin-6 positive cells were significantly higher than those in sham operation group(P<0.01);in the reperfusion time of 6h,12h,24h,48h,72h,Cerebral ischemic preconditioning group rats interleukin-6 positive cells were significantly lower than that of the cerebral ischemia reperfusion model group(P<0.01).6.At the time of reperfusion 6h,12h,24h,48h,72h,the expression of STAT3 and JAK2 immune positive cells were not found in sham operation group;JAK2 in brain tissue of model rats of cerebral ischemia reperfusion,STAT3 positive cells were significantly higher than the sham group(P<0.01);in the reperfusion time of 6h,12h,24h,48h,72h,cerebral ischemic preconditioning in rats of group JAK2,STAT3 positive cells were significantly lower than the model of cerebral ischemia reperfusion group(P<0.01).Conclusion:1.Hyperlipidemia rats with focal cerebral ischemia reperfusion injury could cause the change of brain water content increased,neurological deficit,cerebral ischemia pathological injury.2.The expression of IL-6,JAK2 and STAT3 was up-regulated after focal cerebral ischemia and reperfusion,which may be related to the increase of brain tissue injury.3.Repeated transient limb ischemia preconditioning might through inhibition of JAK2/STAT3 signal transduction pathway and inflammatory cytokines IL-6 and reduce cerebral ischemia and reperfusion injury of brain tissue,brain edema,cerebral infarct volume reduced,alleviate neural dysfunction,thus to protect brain function. |
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