Effect of Isoflurane on Cerebral Injury in Spontaneously Hypertensive Rats through BMP4/Smad Signaling Pathway
Objective:To explore the effect of isoflurane on brain injury in spontaneously hypertensive rats(SHR)by regulating bone morphogenetic protein 4(BMP4)and its downstream Smad protein.Methods:Forty-eight SHR rats were randomly divided into model group,isoflurane group,positive drug group,isoflurane+LDN193189 group,and healthy rats were used as healthy control group,with 12 rats in each group.Rats in each group were placed into oxygen tanks,healthy control group,model group and positive drug group were injected with special gas(30%O2,70%N2)for 1 h,isoflurane group and isoflurane+LDN193189 group were injected with special gas mixed with 2%isoflurane for 1 h,and isoflurane content was detected by anesthesia gas detector.Ensure isoflurane concentration was maintained at 2%at all times.After ventilation,rats in isoflurane+LDN193189 group were intraperitoneally injected with BMP4/Smad pathway inhibitor solution of 20μL(LDN193189,5 mg/kg),the positive drug group was intraperitoneally injected with 20μL(10 mg/kg)of valsartan solution,and the healthy control group,model group and isoflurane group were intraperitoneally injected with the same volume of normal saline water.Oxygen tank ventilation test and injection were once a day for 10 days.The changes of tail artery systolic blood pressure were detected by non-invasive blood pressure detector.Neurological behavior score was used to evaluate behavioral function.Cerebral water content was used to measured the degree of cerebral edema.The histopathological changes and neuronal injury of hippocampus were detected by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)and Nysch staining.Fluorescence quantitative polymerase chain reaction(PCR)and Western Blot were used to detect the mRNA and protein expression levels of BMP4 and Smad2 mRNA and protein in hippocampus.Results:Compared with the model group,the apoptosis of hippocampal nerve cells in isoflurane group,positive drug group and isoflurane+LDN193189 group decreased,the number of nissellite bodies increased,the blood pressure,neurological score,and cerebral tissue water content decreased significantly,and the mRNA and protein expressions of BMP4 and Smad2 increased significantly(P<0.05).Compared with the isoflurane group,the neuronal apoptosis of rats in isoflurane+LDN193189 group increased,the nissellite bodies decreased sharply,the blood pressure,neurological score,and cerebral tissue water content significantly increased,and the mRNA and protein expressions of BMP4 and Smad2 significantly decreased(P<0.05).There was no significant difference between isoflurane group and positive drug group(P>0.05).Conclusion:Isoflurane can reduce SHR cerebral damage by promoting BMP4/Smad signaling pathway.
spontaneous hypertensionbrain damageisofluranebone morphogenetic protein 4Smad protein
万方数据
维普
