BACKGROUND:Postoperative cognitive dysfunction(POCD)is very common in elderly patients.Some Chinese agents for eliminating oxygen-derived free radicals and reducing oxidative stress injury can obviously decrease the error times of the animal models of Alzheimer disease in the water maze test.However,whether they can be used to treat POCD or notis unclear.OBJECTIVE:To observe the changes of leaming and memory abilities and the levels of interleukin-6(1L-6)and tumor necrosis factor alpha(TNF-α)in aging rats after ketamine-induced anesthesia.and investigate the effects of Fufang Shexiang injection which can eliminate oxygen-derived free radicals.DESIGN:A randomized controlled animal study.SETTING:Experimental animal center of Guangzhou University of Traditional Chinese Medicine.MATERIALS:Twenty-eight SD aging rats(20 months old,350-400 g,male or female)randomly divided into 4 groups with 7 rats in each group:control group,ketamine group,ketamine+low-dosage Fufang Shexiang group and ketamine+high-dosage Fufang Shexiang group.Ketamine (Shanghai Zhongxi Pharmaceutical Co Ltd.China,50 mg/Ml,2 Ml/ampule,Batch No.040207);Fufang Shexiang injection(Jiing Weiwei Pharmaceutical Co.,Ltd.,China,2 Ml/ampule,Batch No.20031203)was composed of musk,curcumae,camphol,acori graminei rhizome,agastache rugosa,menthol,bezoar，comu bubali，scutellafia,gardenia,oncha margantifera usta,etc.Enzyme-linked immunoabsorbent assay(ELISA)kit(Jingmei Bio-Tech Co.,Ltd,Beijing,Batch No.20050915).Morris water maze(Upwards Teksystems Co.,Ltd..Beijing).METHODS:The experiment was carried out in the experimental animal center of Guangzhou university of Traditional Chinese Medicine From September to October in 2005.①Grouping and interventions:In the control group,the rats were intraperitoneally injected with saline(4 Ml/kg per day)at 1-6 days:In the ketamine group.ketamine+low and high-dosage Fufang Shexiang groups,the rets were intraperitoneally injected with ketamine on the 1st day,saline(4 Ml/kg perday)and Fufang Shexiang(2 and 6 Ml/kg per day)were intraperitoneally injected at 2-6 days respectively.②There were two parts for the Morris water maze test:Place navigation test:It lasted for 6 days.The rats swam freely for 2 minutes before anesthesia on the 1st day(DO):Rats were placed into from a fixed position to locate the platform after 1 hour of drug injection.The latencv to find the platform was recorded manually with the second stop-clock.The shorter the latency.the better the leaming ability.Spatlal probe test:At D5,after the last navigating experiment.the platform was removed away.The rats were placed Into the water facing against the wall to find the platform again.times of swimming through the quadrant which the platform had ever been in 2 minutes would be recorded.The more the times or the longer the duration,the better the memory.③Determinations of IL-6 and TNF-α in peripheral blood:At D5.IL-6 and TNF-α levels in peripheral blood were measured by ELISA.④Statistical analysis:The t test(within groups) or one-way analysis of vadance(between groups)were applied.HAIN OUTCOME MEASURES:①The escape latency;②The times of swimming through the hidden platform.quadrant after it was removed;③The levels IL-6 and TNF-αin penpheral blood.RESUL TS:Ail the 28 rats were involved in the final analysis.①Escape latency:As time prolonged.the latencles in the control group and ketamine +high-dosage Fufang Shexiang group were gradually shortened (p＜0.05).The latencies in the ketamine group wore all longer than those in the control group except that on the 3rd day(P＜0.05).The latency in the ketamine group on the 4th day was obviously longer than that in the ketamine +high-dosage Fufang Shexiang group [(1.7±0.3),(0.9±0.7)minutes,P＜0.05].The Iatencies in the ketamine group on the 2nd to 5th days+low-dosage Fufang Shexiang group were close to those in the control group (P＞0.05),whereas that on the 6th day was obviously longer than that in the control group [(0.g±0.7).(0.3±0.3) minutes P＜0.05].The latencies in the ketamine+high-dosage Fufang Shexiang group were all close to those in the control group at each time point(P＞0.05).②Swimming times through the quadrant of the hidden platform within 2 minutes after it was removed:The swimming times in the ketamine group and ketamine +low-dosage Fufang Shexiang group were obviously fewet than those in the control group[(2.7±2.1).(2.7±3.2),(4.7±1.8).(5.3±3.8)times,P＜0.05]:Whereas there were no significant differences between the ketamine group and ketamine+low-dosage Fufang Shexiang group(P＞0.05),as well as between the ketamine group and ketamine +high-dosage Fufang Shexiang group(P＞0.05).③Changes of IL-6and TNF-α levels in peripheral blood:The IL-6 level in the controI group was obviously lower than those in the ketamine group and ketamine +low-dosageFufang Shexiang group [(101.08±58.73),(161.121±15.77),(346.42±184.76)ng/L.P＜0.05],but had no obvious difference as compared with that in the ketamine +low-dosage Fufang Shexiang group(P＞0.05):The IL-6 level in the ketamine +high-dosage Fufang Shexiang group was not significantly different from those in the ketamine group and ketamine +low-dosage Fufang Shexiang group (p＞0.05).The TNF-α in the control groupwas obviously lower than those in the other three groups [(53.64±31.4),(96.69±79.34),(151.66±37.50),(141.50±106.85)ng/L,P＜0.05],and there were no significant differences among the latter three roups(P＞0.05).CONCLUSION:Abilities of learning and memory in aging rats were impaired induced by anesthesia with in-traperitoneal injection of ketamine.also accompanied by the increases of IL-6 and TNF-α.Fufang Shexiang injection can ameliorate the impairments.especially that of higher dosage.