ABSTRACT
Objective To investigate the roles of tumor necrosisfactor-α(TNF-α) and nuclear factor-κB (NF-κB) in cerebral ischemia-reperfusion injury in rats w ith diabetes mel itus. Methods Thirty-six healthy male Sprague-Daw ley rats w ere divided into a euglycemic sham operation group, a euglycemic isc hemia-reperfusion group, and a diabetes ischemia-reperfusion group (n=12 in each group) according to a random number table. A diabetes model w as induced by intraperitoneal injection of streptozotocin, and then a focal cerebral ischemia-reperfusion model w as induced by the suture method. The neurological deficit score was performed at 24 h after reperfusion. 2,3,5 triphenyl tetrazolium staining was used to measure the cerebral infarction area. Western blotting w as used to detect the expression levels of NF-κB and TNF-αon the ischemic sides. Results The neurological function scores w ere 0.00 ±0.00, 2.50 ±1.08, and 3.20 ± 1.03, respectively in the euglycemic sham operation, euglycemic cerebral ischemia-reperfusion and diabetes cerebral ischemia-reperfusion groups, and there w ere significant differences (F=38.015, P<0.001). The neurological deficit scores of the diabetes cerebral ischemia-reperfusion group w ere significantly aggravated compared with the euglycemic cerebral ischemia-reperfusion group (P<0.05). The infarct areas of the euglycemic sham operation, euglycemic cerebral ischemia-reperfusion and diabetes cerebral ischemia-reperfusion groups w ere 0.00% ±0.00%, 33.09% ±5.17%, and 55.45% ±9.29%, respectively, and there w ere significant differences among the groups (F=206.614, P<0.001), in w hich the infarct area in the diabetes cerebral ischemia-reperfusion group w as enlarged significantly compared w ith the euglycemic cerebral ischemia-reperfusion group ( P< 0.05 ). At 24 h after reperfusion, there w ere no significant differences in the expression levels of the cortical NF-κB (F=29.993, P<0.001) and TNF-α(F=28.722, P<0.001) on the ischemic sides in each group, in w hich the expression levels of NF-κB and TNF-αin the diabetes cerebral ischemia-reperfusion group w ere increased significantly compared w ith the euglycemic cerebral ischemia-reperfusion group (al P<0.05). Conclusions Diabetes may aggravate cerebral ischemia reperfusion injury. The upregulated expression of TNF-αand NF-κB may be one of the mechanisms of diabetes aggravating cerebral ischemia-reperfusion injury.
ABSTRACT
AIM:To evaluate the effect of microRNA-155(miRNA-155) on the regulation of angiogenesis in diabetic rats with cerebral ischemic injury .METHODS: Adult male Sprague-Dawley rats were randomly divided into 5 groups:sham group, cerebral ischemia group , diabetic cerebral ischemia group , diabetic cerebral ischemia +miRNA-155 inhibitors group and diabetic cerebral ischemia +scramble group .Diabetes model was made by injection of streptozocin and permanent cerebral ischemic model was developed by suture-occluded method .The scores of neurological deficit and infarct volume were estimated at 24 h after cerebral ischemia .miRNA-155 level was detected by real-time polymerase chain reaction.The expression of platelet endothelial cell adhesion molecule-1 ( PECAM-1/CD31 ) and vascular endothelial growth factor ( VEGF) was detected by Western blotting .RESULTS:miRNA-155 inhibitor significantly reduced miRNA-155 levels in the ischemic cortex (P<0.05), improved the scores of neurological deficit , reduced infarction size and up-regulated the levels of CD31 and VEGF (P<0.05).CONCLUSION:miRNA-155 has a critical role in the regulation of angiogenesis in diabetic rats with cerebral ischemia .Down-regulation of miRNA-155 using miRNA-155 inhibitor attenuates brain infarct injury in diabetic rats .
ABSTRACT
Lipoxin A4 is an arachidonic acid metabolite,it is an important endogenous anti-inflammatory mediators in the body,which is known as an inflammatory braking signal. Inflammatory response is an important factor for causing cerebral ischemia-reperfusion injury.Lipoxin A4 can exert neuroprotective effects by inhibiting inflammatory response.In addition,lipoxin A4 can also reduce blood-brain barrier permeability,reduce cerebral edema,and promote recovery of neurological function.This article reviews the neuroprotective roles and mechanisms of lipoxin A4 in cerebral ischemia-reperfusion.
ABSTRACT
Objective To investigate the protective effect of lipoxin A4 on diabetic rats with focal cerebral ischemia-reperfusion and its mechanisms.Methods Thirty-six adult male Sprague-Dawley rats were randomly divided into a sham operation group,a cerebral ischemia-reperfusion group,and a lipoxin A4 group (n=12 in each group).Diabetes was induced by repeated intraperitoneal injection of low-dose streptozotocin.A model of middle cerebral artery occlusion and reperfusion was induced by the intraluminal suture method.Five minutes after cerebral ischemia,lipoxin A4 0.03 nmol/5 μ1 was injected via intracerebroventricular in the lipoxin A4 group.The other groups were injected equal volume of saline.Two hours after ischemia,the suture was pulled out and reperfusion was achieved.Neurological deficit scores were performed at 24 hours.Then the rats were decapitated and their brains were taken out.2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to detect infarct size.Western blotting was used to detect the expression of cortical tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB).Results The neurological deficit score showed that no neurological deficit was observed in the sham operation group (score 0).The neurological deficit score in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (2.20 ± 1.03 vs.3.20 ± 1.03; P ＜0.05).TTC staining showed that no infarct was observed in the sham operation group.The infarct size in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (27.52％ ± 5.71％ vs.55.45％ ± 9.29％ ; P ＜0.05).Western blotting showed that the expression levels of TNF-α in the sham operation,cerebral ischemiareperfusion,and lipoxin A4 groups were 0.64 ± 0.16,1.85 ± 0.52,and 1.40 ± 0.34,respectively.There were significant differences among the 3 groups (F =18.868,P ＜0.001).The expression level of TNF-α in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (P ＜0.05).The expression levels of NF-κB in the sham operation,cerebral ischemia-reperfusion and lipoxin A4 groups were 0.79 ±0.24,2.09 ± 0.47,and 1.27 ± 0.35,respectively.There were significant differences among the 3 groups (F =16.736,P ＜ 0.001).The expression level of NF-κB in the lipoxin A4 group was significantly lower than that in the cerebral ischemia-reperfusion group (P ＜0.05).Conclusions Lipoxin A4 has certain protective effect on focal cerebral ischemia-reperfusion injury in diabetic rats,its mechanism may be associated with the inhibition of the expression of TNF-α and NF-κB.