| Background: Alzherimer’s disease is a common type of nervous systemdegenerative disease in the elderly, its incidence is second only to heart disease,cancer and cerebrovascular disease and increasing year by year. China is one ofthe world’s most populous country, is also a large elderly population that theaging of the population over60years is more than120million, dementiaprevalence is3~8%, of which more than60percent of Alzheimer’s patients,accounts for about a quarter of the number of cases in the world, with the furtherexacerbate China’s aging population, the number of patients will reach20million in the further50years. Alzheimer’s disease for the patient’s family andthe society as a whole has caused heavy mental and economic burden. Therefore,the strengthening of Alzheimer’s disease research, resolve existing etiology isunknown, high morbidity, high mortality, there is no effective treatmentmeasures and other issues, has important scientific and social significance.Recent studies show that protein aggregation accompanied by neuronaldegeneration in Alzheimer’s disease is an important pathological processes,apoptosis and autophagy are closely related to the pathogenesis of Alzheimer’sdisease. Some studies show that general anesthesia can reduce the incidence ageof Alzheimer’s disease and increase its incidence, it is closely related toAlzheimer’s disease. Inhaled anesthetics isoflurane is one of common drugs usedin clinical, which has been reported that clinical relevant concentrations may neuronal apoptosis, so that mediated occurrence of Alzheimer’s disease. But itsprecise signaling pathways and regulatory mechanisms remain to be furtherstudy, then provide guidance for clinical work.Purpose: To explore the effect of isoflurane on autophagy and apoptosisproteins of rat PC12cells induced by A25-35, and to elucidate the mechanismsunderlying the effect of isoflurane on autophagy.Methods: PC12cells were randomly divided into4groups (n=6each).Group control (group C): PC12cells were administered with normal medium;Group A25-3510μmol/L (group A): PC12cells were administered withA25-3510μmol/L; Group2%isoflurane (group Iso): PC12cells wereadministered with2%isoflurane; Group2%isoflurane and A25-3510μmol/L(group Iso+A): PC12cells were administered with2%isoflurane+A25-3510μmol/L. All the PC12cells in each group were performed with followingprotocol: autophagosomes in PC12cells were examined by transmissionelectron microscope, the expression of autophagy associated protein LC3-II, p62and autophagic signal gene mTOR, Beclin-1were detected by western blotanalysis after6h of drugs administration; cell viability was determined by MTTassay, western blot was performed to observe the expression of apoptosisassociated protein Bcl-2and Caspase-3after24h of drugs administration.Results: Compared with group C, great amounts of autophagosomes werepresented in PC12cells of group A, expression of LC3-II, Beclin-1and Caspase-3were significantly increased (P<0.05) and expression of p62,p-mTOR and Bcl-2decreased significantly as well as cell survival rate (P<0.05).However, autophagosomes failed to be presented in PC12cells of group Iso,expression of LC3-II, Beclin-1and Bcl-2as well as cell survival rate weresignificantly decreased (P<0.05) and expression of p62, p-mTOR and Caspase-3increased significantly (P<0.05). Compared with group A, only a fewautophagosomes were found in PC12cells of group Iso+A, expression ofLC3-II and Beclin-1as well as cell survival rate were significantly decreased(P<0.05), and expression of p62, p-mTOR and Caspase-3increased significantly(P<0.05), but nothing changes occurred with expression of Bcl-2(P>0.05).Conclusion: Isoflurane inhibits autophagy and aggravate expression ofapoptosis proteins of rat PC12cells induced by A25-35through activation ofautophagic signal gene mTOR and inhibition of Beclin-1. |
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