| Background:Acute cerebral ischemia is a common clinical cerebrovascular disease,characterized by high incidence,high disability and high mortality.Ischemic cerebrovascular disease is 4 times as high as hemorrhagic cerebrovascular disease.Hypertension,hyperlipidemia and diabetes are the main risk factors for ischemic cerebrovascular disease.No matter what kind of risk factors causes cerebral vascular obstruction which lead to acute cerebral ischemia,the restoration of cerebral blood flow as early as possible to alleviate the ischemic neuronal damage is the most effective therapy,but the recovery of blood flow will aggravate the damage of cerebral ischemic/reperfusion(I/R)injury.The current mechanism of I/R injury may be related to Ca2+ overload,free radical damage,excitatory amino acid toxicity,and energy metabolism disorder,which are involved in endoplasmic reticulum stress.It shows that Apelin is involved in the whole process of neuron endoplasmic reticulum stress.It is of great practical significance and wide application prospect to study the role and mechanism of Apelin in acute ischemic reperfusion injury.So the changes in ERS-related proteins may help to understand I/R injury.Objective:To investigate the effects of Apelin-36 on the model of cerebral ischemic stroke and analyze the metabolic pathway and possible metabolic mechanism,Apelin-36 was injected into lateral ventrical in the transient middle cerebral artery occlusion(MCAO)of rats.The different doses of Apelin-36 were investigated to affect cerebral ischemic penumbra.We evaluated the effects of Apelin-36 on the cerebral infarction and expression of related apoptotic proteins,and explored the effects of Apelin-36 on the apoptosis by regulating ERS.Methods:The male Wistar rats(210 g ± 10g)were divided into sham group,control group and drug group(Apelin-36 group and Apelin-13 group).Ischemia time was 2h and reperfusion time was 24h.The sham group was only exposed the carotid artery without suture.Infarct size was determined by TTC staining method and the apoptosis was observed by TUNEL method.CHOP,Cleaved-caspase-3,and GRP78 protein were detected by Western-Blot.Real-time PCR was used to detect CHOP mRNA,Cleaved-caspase-3 mRNA and GRP78 mRNA expression.The values were represented by mean ±SEM.One-way ANOVA followed by Tukey test was performed by using GraphPad Prism.The difference between the two groups was clear.P<0.05 was considered statistically significant.Results:(1)The rat artery occlusion model was established successfully.In the model group,the area of cerebral infarction was increased compared with the sham group(P<0.001),but the infarct volume was significantly reduced when Apelin-36 intervention group compared with model group,indicating that Apelin-36 significantly reduced the infarction area of rats;(2)GRP78 mRNA,CHOP mRNA,and Cleaved-caspase-3 mRNA were detected by ischemic penumbra.The expression of GRP78 mRNA,CHOP mRNA,and Cleaved-caspase-3 mRNA were significantly increased in the model group compared with the sham operation group(P<0.05).Compared with the model group,Apelin-36 significantly decreased the expression of GRP78 mRNA,CHOP mRNA,and Cleaved-caspase-3 mRNA(P<0.05);(3)GRP78,CHOP,and Cleaved-caspase-3 protein were detected in the ischemic penumbra zone,and the expression of GRP78,CHOP,Cleaved-caspase-3 protein in the model group were increased compared with the sham group(P<0.05).Compared with the model group,Apelin-36 significantly reduced the expression of GRP78,CHOP,and Cleaved-caspase-3 protein(P<0.05).(4)The number of apoptotic cells was detected by TUNEL staining.Compared with the sham group,the number of apoptotic cells in the model group was significantly increased than that in the sham group(P<0.0001).The number of apoptotic cells in the Apelin-36 group was significantly lower than that in the model group,and the number of apoptotic cells in Apelin-36 group was significantly lower than that in the model group(P<0.05).Conclusion:Apelin-36 has the neuroprotective effects on ischemic reperfusion model.Apelin-3 6 significantly reduced cerebral infarction area induced by I/R injury,the number of apoptotic cells and the expression of GRP78,CHOP,Cleaved-caspase-3 at mRNA and protein level,respectively.Its neuroprotective mechanism may be related to the inhibition of ERS. |
PDF Full Text Request