Protective Effects Of Liraglutide On Focal Cerebral Ischemic Injury With Diabetes Mellitus Rat By Activating PPARs

Objective: To observe the effect of liraglutide on the expression of peroxisome proliferator-activated receptors(PPARs)in the brain tissue of diabetic rats after cerebral ischemia injury,and to further investigate the effect of liraglutide on cerebral ischemic injury with diabetes mellitus and the potential mechanism.Methods: Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: sham-operated group(Sham group),diabetes cerebral ischemia group(DCI group),liraglutide-pretreatment DCI group(Lir group)and insulin-pretreatment DCI group(Ins Group),with 12 rats in each group.Diabetes was induced by intraperitoneal injection of streptozotocin,and a model of permanent middle cerebral artery occlusion(MCAO)was established in the diabetic rats.The rats in the Lir group and Ins group were intraperitoneally injected with liraglutide(100 ?g/kg,q12h)and insulin(2 IU/kg,q12h),respectively,7 days before MCAO,while the other groups were injected with an equal volume of normal saline during the same period of time.Neurological deficit scores were determined at 24 hours after MCAO.Then the rats were decapitated,and their brains tissues were taken out to measure the infarct area by TTC staining.Western blotting was used to detect the expression in the ischemic area PPAR?(peroxisome proliferator-activated receptor ?),PPAR?,PPAR?,NF-?Bp65,TNF-?.Results:(1)Fasting blood glucose changes:There was no significant difference in blood glucose between the Sham group,DCI group,Lir group and Ins group before drug intervention.There was a significant difference in blood glucose levels between the groups after drug intervention(F=23.44;P=0.000).The Lir group and Ins group showed significant reductions in blood glucose after injection of liraglutide or insulin,the differences were statistically significant(P=0.000;P=0.000);The blood glucose unchanged in the Sham group and DCI group after the injection saline.(2)Neurological deficit score:compared with the DCI group,the Ins group didn't significantly changed in neurological deficit score,but the Lir group showed a significant reduction in neurological deficit score(P=0.000);compared with the Lir group,the ins group was significantly increased(P=0.000).(3)Cerebral infarction volume: compared with the DCI group,the Ins group didn't significantly changed in infarct volume,but the Lir group showed a significant reduction in infarct volume(P=0.000);compared with the Lir group,the Ins group was significantly increased(P=0.000).(4)The expression levels of PPAR?,PPAR?,PPAR?: compared with the Sham group,the DCI group showed significant increase in the expression of PPAR?,PPAR? and PPAR?(P=0.026;P=0.007;P=0.019);compared with the DCI group,the Ins group didn't significantly changed in the expression of the above proteins,but the Lir group was significantly increased(P=0.000;P=0.000;P=0.000).(5)The expression levels of NF-?Bp65 and TNF-?:compared with the Sham group,the DCI group showed significant increase in the expression of NF-?Bp65 and TNF-?(P=0.000;P=0.000);compared with the DCI group,the Ins group didn't significantly changed in the expression of the above proteins,but the Lir group was significantly increased(P=0.000;P=0.000).Conclusion: Liraglutide treatment significantly decreases glucose levels of diabetic rats,and it has a certain neuroprotective effect against focal cerebral ischemic injury in diabetic rats.It appears that the protective effect of liraglutide against focal cerebral ischemic injury in diabetic rats,possibly by up-regulation of PPAR?,PPAR?,PPAR?expression and down-regulation of NF-?Bp65 and TNF-? expression.