| Objective :To observe the effects of liraglutide on the expression of nuclear factor erythroid 2-related factor(Nrf2)/heme oxygenase-1(HO-1)signaling in diabetic rats with focal cerebral ischemia,and to further investigate the protective effects and potential mechanism of liraglutide on the diabetic rats with cerebral Ischemia injury.Methods: Sixty-four adult male Sprague-Dawley rats were randomly divided into 4groups :sham-operated group(S group),cerebral ischemia group(CI group),diabetes mellitus ischemia group(DCI group)and liraglutide-pretreatment diabetes ischemia group(Lir group),n=16.Diabetes model was made by intraperitoneal injection of streptozotocin(STZ)and cerebral ischemia model was developed by longe suture occluded method in middle cerebral artery of diabetic rats.The Lir group was given abdominal cavity injection of liraglutide at 100 g/kg,every 12 h for 7 days before MCAO.The rats in the S group,CI group and Lir group were injected with an equal volume of normal saline.At 48 h after middle cerebral artery occlusion(MCAO),neurological deficits and infarct volume were evaluated.Oxidative stress was assessed by determination of superoxide dismutase(SOD)activities.The expression levels of Nrf2 and HO-1 were analyzed by Western blotting.Results:(1)The tail vein blood glucose change at each experimental group after the injection drug.In the Lir group blood glucose was(28.33±7.36)mmol/L after the injection STZ drug,The blood glucose was(21.30±7.36)mmol/L after the injection liraglutide drug.There was a significant before and after injection,The differences were statistically significant(P<0.05).In the DCI group the blood glucose was(27.31±4.22)mmol/L,The blood glucose was significantly increased,The differences were statistically significant(P<0.05).The blood glucose unchanged in the S group,CI group and DCI group after the injection saline.(2)The neurological deficit score: The neurological deficit scores was(2.83±0.41)in the Lir group,(3.50±0.55)in the DCI group,(2.17±0.41)in the CI group,and(0.00±0.00)in the S group.Compared with S group,The neurological deficit scores in the CI group and DCI group were significantly increase;Compared with the CI group,The neurological deficit score in the DCI group was significantly higher(P<0.05);Compared with DCI group,The neurological deficit score in the lir group was significantly lower.(P<0.05).(3)The average infarct volume: the average infarct volume was(32.27±2.13)% in the Lir group,(38.40±5.85)% in the DCI group,(31.11±1.58)% in the CI group,and(0.00±0.00)in the S group.Compared with S group,The infarct volume in the CI group and DCI group were significantly increase;Compared with the CI group,The infarct volume in the DCI group was significantly higher(P < 0.05);Compared with DCI group,The infarct volume in the lir group was significantly lower(P < 0.05).(4)Determination of SOD enzyme activity,the determination of SOD enzyme activity was(134.51±14.42)in the Lir group,(103.33±9.70)in the DCI group,(140.80±15.21)in the CI group,and(153.28±13.41)in the S group,Compared with S group,The SOD enzyme activity levels in the CI group and DCI group were significantly descend;Compared with the CI group,The SOD enzyme activity levels in the DCI group was significantly lower(P<0.05);Compared with DCI group,The SOD enzyme activity levels in the lir group was significantly higher(P<0.05).(5)The expression of Nrf2 protein,the expression of Nrf2 protein(0.74±0.05)in the Lir group,(0.61±0.07)in the DCI group,(0.87±0.15)in the CI group,and(0.54±0.06)in the S group,Compared with S group,the Nrf2 protein expression levels in the CI group and DCI group were significantly up-regulation;Compared with the CI group,The Nrf2 protein expression levels in the DCI group was significantly down-regulation;Compared with DCI group,The Nrf2 protein expression levels in the lir group was significantly up-regulation(P < 0.05).(6)The expression of HO-1 protein,the expression of HO-1 protein(0.74±0.05)in the Lir group,(0.61±0.07)in the DCI group,(0.87±0.15)in the CI group,and(0.54±0.06)in the S group,Compared with S group,the HO-1 protein expression levels in the CI group and DCI group were significantly up-regulation;Compared with the CI group,The HO-1protein expression levels in the DCI group was significantly down-regulation;Compared with DCI group,The HO-1 protein expression levels in the lir group was significantly up-regulation(P<0.05)Conclusion:1.Further confirmed diabetes can aggravate the local cerebral ischemic injury in SD rats.2.Nrf2/HO-1 signaling Pathway plays an important role in Diabetes Mellitus complicated with Cerebral Ischemia injury 3.It appears that the protective effect of liraglutide on brain nerve cells in diabetes complicated with cerebral ischemia injury may be through the activation and up-regulation of the Nrf2/HO-1 signaling pathway. |
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