Effects Of Inhaled Anesthetic Isoflurane On Apoptosis And Endoplasmic Reticulum Stress Induced By Aβ25-35in Rat PC12Cells

Background: Accompained by acceleration of the process of agingpopulation, alzheimer’s disease has become one of the important disease threatto human health in the21st century, because of its pathogenesis is complex, highmorbidity, high mortality and there is no effective treatment measures, so itsrelated fields has become the research focus in the scientific community. Inrecent years, many studies have shown a close link between protein aggregationand neuronal injury and death, at the same time, apoptosis is closely related toAlzheimer’s disease, but the mechanism is not yet very clear, may be associatedwith mitochondrial damage, oxidative stress, calcium homeostasis and otherfactors. Meanwhile, the researchers found that it is the more sensitive theendoplasmic reticulum to the change of internal environment, when the cellsstimulated by certain internal and external factors, the cells start endoplasmicreticulum stress mechanism, but a long, sustained endoplasmic reticulum stressactivates the cell death cascade, and thus participate in the pathogenesismechanisms and pathological processes of Alzheimer’s disease. Clinical andanimal studies have shown that general anesthesia can aggravate the symptomsof alzheimer’s disease and pathological process, and reduce the onset age,increase its incidence. Inhaled anesthetics isoflurane is one of the most commondrugs used in clinical. Related literature show that inhaled anesthetic isofluranemay activate the apoptotic cascade signaling pathway through the generation and accumulation of abnormal proteins, induced neuronal apoptosis, thenmediated Alzheimer’s disease. Currently230million people worldwide sufferinganesthesia and surgery each year, including Alzheimer’s disease patientsreceiving anesthesia800million or more, there is a huge security and anestheticrisks. Therefore, to explore the relationship among inhaled anestheticisoflurane，alzheimer’s disease and cell apoptosis of inner link has importantclinical and social significance.Purpose: To explore the effect of isoflurane on apoptosis and endoplasmicreticulum stress induced by A25-35in rat PC12cells and to clarify themechanisms.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: cell viability was determined by MTT assay, morphological changes ofapoptotic PC12cells was detected by Hoechst33342staining, western blot wasperformed to observe the expression of molecular chaperone GRP78andendoplasmic reticulum stress associated apoptosis signal protein CHOP, JNKand Caspase-12after24h of drugs administration. Results: Compared with group C, cell survival rate decreased significantlyin group A and group Iso (P<0.05), cell apoptosis rate was significantlyincreased (P<0.05), expression of molecular chaperone GRP78and endoplasmicreticulum stress associated apoptosis signal protein CHOP, JNK and Caspase-12increased significantly (P<0.05). Compared with group A, cell survival ratedecreased significantly in group Iso+A (P<0.05), cell apoptosis rate wassignificantly increased (P<0.05), expression of molecular chaperone GRP78andendoplasmic reticulum stress associated apoptosis signal protein CHOP, JNKand Caspase-12increased significantly (P<0.05).Conclusion: Isoflurane could aggravate apoptosis of rat PC12cellsinduced by A25-35, and its potential mechanisms are involved in activation ofendoplasmic reticulum stress and endoplasmic reticulum stress associatedapoptosis signal pathway.