The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus

Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear.In this study,we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats.Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin.Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery.Post-conditioning comprised three cycles of ischemia/reperfusion.Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion,the structure of the brain was seriously damaged in the experimental rats compared with normal controls.Expression of Bax,interleukin-6,interleukin-8,terminal deoxynucleotidyl transferase d UTP nick end labeling,and cleaved caspase-3 in the brain was significantly increased,while expression of Bcl-2,interleukin-10,and phospho-glycogen synthase kinase 3 beta was decreased.Diabetes mellitus can aggravate inflammatory reactions and apoptosis.Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes.Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta.According to these results,glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

Inhibition of cerebral ischemia/reperfusion injuryinduced apoptosis:nicotiflorin and JAK2/STAT3 pathway

Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.

Effect of electroacupuncture on gene expression in calcium signaling pathway in hippocampal cells in mice with cerebral ischemia reperfusion

OBJECTIVE:To observe the regulation of electroacupuncture on gene expression at calcium signaling pathways in mice with cerebral ischemia reperfusion.METHODS:Sixty male, inbred Kunming mice were randomly assigned to three groups:repeated cerebral ischemia reperfusion group(RG, n = 24),sham-operated group(SG, n = 12), and electroacupuncture group(EG, n = 24).Mice in RG and EGgroups were modeled by repeated cerebral ischemia reperfusion surgery, and EG mice were treated with electroacupuncture for 30 min after recovery from anesthesia.Changes in gene expression profile of mice hippocampi were analyzed by global expression profile microarray.Genes that were up-regulated or down-regulated greater than 1.5folds were considered to be biologically meaningful.Real-time quantitative polymerase chain reaction(q-PCR) method was used to verify the expression of selected genes based on the algorithm [2^(ΔΔCt)].RESULTS:Compared with SG mice, 242 genes showed different in expressions in RG mice:107down-regulated and 135 up-regulated.Compared with RG mice, 609 genes showed a difference of expression in EG mice:315 down-regulated and 375up-regulated.Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated two pathways:calcium signaling and long-term potentiation in which 11 differentially expressed genes selected.Six of the 11 genes in the calcium signaling pathway were verified after real-time q-PCR testing.CONCLUSION:Electroacupuncture treatment of cerebral ischemia reperfusion appears to regulate Atp2a2, Cacna1 e, Camk2 a, Gnas, Grm1, Rapgef3 genes in the calcium signaling pathway.