RESUMO
OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.
RESUMO
Objective To investigate the effect of isoflurane anesthesia on the expression of amyloid β protein (Aβ) in hippocampus in aged rats.Methods Sixty-one healthy male SD rats,aged 18-19 months,weighing 400-500 g,were randomly divided into 3 groups:isoflurane group (group Ⅰ,n =31),control group (groupⅡ,n =20),and blank group (group Ⅲ,n =10).Group Ⅰ inhaled 1.4％ isoflurane for 2 h,and cognitive function was assessed at 5 d before and 2 d after anesthesia by Morris water maze.Group Ⅱ received Morris water maze text only.Group Ⅲ received no treatment.Group Ⅰ was divided into 2 subgroups according to whether the cognitive impairment occurred:cognitive impairment group (P subgroup) and no cognitive impairment group (NP subgroup).The animals were sacrificed immediately after the test.The hippocampus was isolated for determination of the levels of Aβ40 and Aβ42,β-secretase (BACE),insulin degrading enzyme (IDE)and neprilysin (NEP).Results There was no significant difference in the results of Morris water maze test before anesthesia among the 3 groups.There was no significant difference in the swimming velocity between group Ⅰ and group Ⅱ.The time of staying at the original platform quadrant was significantly shorter in P subgroup than in NP subgroup and Ⅱ group,and there was no significant difference in the time of staying at the original platform quadrant between NP subgroup and Ⅱ group.There was no significant difference in the levels of Aβ40 and Aβ42,BACE,NEP and IDE among the 5 groups,and between P subgroup and NP subgroup.Conclusion Isoflurane anesthesia has no effect on the expression of Aβ in the hippocampus,indicating that isoflurane-induced cognitive impairment is not related to Aβ pathway in aged rats.