| Objective:To explore the timing and duration of POCD induced by splenectomy in aged SD rats,to investigate the ameliorative effect of lidocaine on the learning and memorydysfunction and to determine the optimal dose of lidocaine to improve POCD in agedSD rats.Methods：Using statistical software CHISS, the50aged SD rats, were randomly divided intofive groups, namely groups: control group, POCD model group, the lidocaine group(1mg/kg/h), lidocaine group (2mg/kg/h), lidocaine group (4mg/kg/h), n=10. After fiveconsecutive days to get the spatial acquisition, the aged SD rats in each group weredisposed by surgery or infusion of lidocaine at the6th day. At1,3,7,14days aftertreatment all aged rats were tested by the Morris water maze for spatial memory.Results：According to spatial acquisition, ability of learning and memory in all aged ratsgradually enhanced (P <0.01), and kept stable in the first five days, and no significantdifference between the groups every day.About reference memory test results, compared with the control group, in POCDmodel group and lidocaine group (4mg/kg/h) reference memory significantlydecreased (P <0.05); compared with the POCD model group, lidocaine group(1mg/kg/h) and lidocaine group (2mg/kg/h) reference memory significantly increased(P <0.05). About working memory test results, compared with the control group, in POCDmodel group, lidocaine group (1mg/kg/h) at1,3days after treatment, lidocaine group(4mg/kg/h) at1,3,7days after treatment, working memory were significantlydifferent (P <0.05); compared with the POCD model group, in lidocaine group (1,2mg/kg/h) at1,3days and lidocaine group (4mg/kg/h) at1day after treatment, workingmemory were significantly different (P <0.05).Conclusion：POCD model can be successfully build by splenectomy under anesthesia. Spatialmemory was obviously damaged at3day after surgery and returned to normal at7day after surgery. In the perioperative period, continuous infusion of1mg/kg/hlidocaine for1h in the tail vein can improve the spatial memory of aged rats withPOCD obviously. Therefore,1mg/kg/h is the best dose of lidocaine to improve POCDin aged rats.PartⅡ The effect of the optimal dose of lidocaine on inflammation in thehippocampus and blood plasma of aged rats with POCDObjective:By molecular biology and immunohistochemical techniques, to observe the effect ofthe best dose of lidocaine on inflammation in hippocampus and peripheral blood ofthe aged rats with POCD, and to explore its important role involved in modulating thechange beween expression of the central or peripheral inflammation and activationand expression of hippocampal astrocytes.Methods:After ensuring dose-effect relationships and the optimal dose of lidocaine, usingstatistical software CHISS, the72aged SD rats, were randomly divided into threegroups, namely groups: control group, POCD model group, the lidocaine group(1mg/kg/h).54aged SD rats were tested by Morris water maze, n=18. After fiveconsecutive days to get the spatial acquisition, the aged SD rats in each group were disposed by surgery or infusion of lidocaine at the6th day. At1,3,7days aftertreatment all aged rats were tested for spatial memory.18aged SD rats were tested bythe object recognition test, n=6. At1st day after treatment all aged rats were tested fornon-spatial memory. At1,3,7days after treatment, inflammatory cytokines weredetected by ELISA in hippocampal tissues and peripheral blood plasmas in all of theaged rats. By immunofluorescence technique and western blot, activation ofastrocytes and expression of GFAP were observed in hippocampus of all aged rats.Results：After ensuring the optimal therapeutic dose of lidocaine1mg/kg/h, not only spatialmemory was evaluated by the Morris water maze test in all aged rats, but alsonon-spatial memory was evaluated by object recognition test. In object recognitiontest, compared with the control group, identification index in POCD model group wassignificantly different (P <0.05); compared with the POCD model group,identification index in lidocaine group (1mg/kg/h) was significantly different (P <0.05).About pro-inflammatory cytokines, compared with the control group, in POCDmodel group, concentrations of TNF-α, IL-1β and IL-6were significant different at1,3days after treatment in the hippocampus and plasma respectively (P <0.05);compared with the POCD model group, in lidocaine group(1mg/kg/h), concentrationsof TNF-α, IL-1β and IL-6were significantly different at1,3days after treatment inthe hippocampus and plasma respectively (P <0.05). About anti-inflammatorycytokine, compared with the control group, in POCD model group, the concentrationof IL-10was significantly different at1,3days after treatment in the hippocampus andplasma respectively (P <0.05); compared with POCD model group, the concentrationof IL-10in lidocaine group (1mg/kg/h) was significantly different at3day aftertreatment in the hippocampus and plasma (P <0.05).In the results of immunofluorescence staining and western blot, compared with thecontrol group, in POCD model group, expression of GFAP was significantly different at1,3days after treatment in hippocampus (P <0.05), and immunofluorescenceintensity of GFAP increased; compared with the POCD model group, the expressionof GFAP in lidocaine group (1mg/kg/h) was significantly different at3days aftertreatment in hippocampus (P <0.05), and immunofluorescence intensity of GFAPwas significantly decreased.Conclusion：In the perioperative period, continuous infusion of1mg/kg/h lidocaine for1h in thetail vein can improve the spatial memory and non-spatial memory of aged rats withPOCD obviously, and well controll inflammatory cytokines (includingpro-inflammatory cytokines and anti-inflammatory cytokines) in hippocampus andplasma of aged rats.1mg/kg/h lidocaine can significantly reduce activation ofastrocytes and expression of GFAP at1,3day after surgery in hippocampus of agedrats with POCD. |
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