Effects Of Isoflurane On Cognition And Neurocyte Apoptosis Of Brain In Aged Rats

Objective The incidence of postoperative cognitive obstruction is not obviously descent,the reason is that the mechanism is still unclear. This experiment investigate the effect of different isoflurane on aged rats' cognition,then observe the neurocyte apoptosis of hippocampus and cortex in brain.We hope to give some contribution in the research of aged rats' cognitive changes which caused by isoflurane,so as to achieve some guidences to make use of isoflurane safely in clinic.Methods Selecting 69 22-24-month-old SD rats which fit to the experiment,and randomly divide them into three groups:group oxygen,group 1.2%isoflurane and group 1.8%isoflurane.The 21 rats in group oxygen only inhale mixed gas containing 40%oxygen for three hours. The 24 rats in each group Iso are induced by inhalating 3%isoflurane, after body-righting reflex disappeared(about 10±2 min).We use correspond concentration(1.2%or 1.8%)to maintain anesthesia for 3 hours.The flow rate of inspired oxygen is 2L/min during the course of anesthesia,and we monitor the concentration of oxygen is 40%.We randomly draw 3 rats for monitoring vital sign by femoral artery puncture during the course of anesthesia.Let the rats naturally wake up after anesthesia.Then each group rats are randomly divided into two parts: One part only carry out the ethology observation(12rats per group);The other part carry out the neurocyte apoptosis experiment(9rats per group). Selecting 12 rats randomly through each group,and then using Morris water maze to carry out the ethology observation from 24 hours to the 7^th day after anesthesia.Training 4 times every day from the 1^stday to the 6^th day,and record the average escape latency which is the time that the rats get to the platform,being took as the rats' learning results.On the 7^thday, we remove the platform to carry out space exploration experiment,and observe the changes of the rats' learn-remember capability.Three rats are randomly selected from each group at 24h,72h and 7d after anesthesia, then dabbled,removed brain,fixed and sectioned(contain hippocampus). By means of TUNEL method in situ end-labeling to detect the neuron apoptosis of hippocampus and cortex in brain.Results①The results of water maze:the average escape latency of group 1.2%Iso and 1.8%Iso at the 2^nd,3^rdday are[(44.16±17.91),(26.80±11.51)]和[(47.41±20.94),(27.08±11.64)],which are more than group oxygen[(23.61±13.91),(14.87±8.37)(P＜0.05),the 2^ndday difference is more obviously(P＜0.01).But there is no significant difference between the different concentration of inhalating isoflurane. There is no difference at the exploration experiment on the 7^thday.①.The results of neurocyte apoptosis:There is no significant difference of the neurocyte apoptosis rate in the CA1,CA2 and CA3 parts of hippocampus between the group Iso and group oxygen(P＞0.05).But the 24hours' neurocyte apoptosis rate in cortex of group 1.2%Iso and 1.8% Iso are[(6.09±1.42)%,(8.42±1.30)%];the 72hours' neurocyte apoptosis rate are more obvious[(12.36±1.38)%,(14.34±1.27)%];on the 7^thday,the neurocyte apoptosis rate are less than before[(5.84±1.26)%,(7.23±1.08)%],but those results have significant difference comparing with the result of group oxygen[(0.15±0.31)%,(0.17±0.30)%,(0.12±0.26)%].There is significant difference of the neurocyte apoptosis rate of cortex between the group 1.8%Iso and the group 1.2%Iso(P＜0.01).Conclusion Isoflurane anesthesia may result in cognitive impairment transiently in the aged rats,but the change almost recovery on the 4^thday after anesthesia.By means of TUNEL method,we found that isoflurane induce the neuron apoptosis of cortex in aged rats' brain; but at present we can't draw the final conclusion that the postoperative cognitive obstruction which caused by inhalting isoflurane is relate to the neuron apoptosis of cortex.