| Cognitive dysfunction is a common neurological complication after the surgery and anesthesia, which has become a major problem of eldly, affecting the postoperative recovery process and the quality of life. Although sevoflurane is one of the common clinical use inhaled anesthetics and has an effect on postoperative cognitive function, the mechanism is still unclear. Therefore, to insight the mechanism and to investigate the appropriate depth, which may reduce or even eliminate the occurrence of cognitive dysfunction, has been the hotspot and difficulty of anesthesiology research. Several studies show that inflammation reaction of the central nervous systerm reduced by surgery and anesthesia may be involved in the process. Interference of the central nervous system inflammatory response can improve cognitive function and reduce the incidence of POCD. Glial cell is an important part of the inflammatory response in CNS. Glial cell can release inflammatory factors and change the morphology of its own after being activiated, which can induce inflammatory response in CNS. By this way, the glia cell can fire a neuro-toxicity directly or indirectly through the inflammatory response, and affect cognitive function in turn. Excessive proliferation of astrocytes can inhibit the axon regeneration and injure nerve tissue. Excessive activation of microglia can destroy neighboring neurons by producing and releasing neurotoxic substances. A certain concentration of sevoflurane inhaled can improve cognitive function, but the opinions of some other teams are opposite. Therefore, we assume that sevoflurane may have an effect on cognitive function by activating glial cells of hippocampus and may release inflammatory factors which involved in the central nervous system inflammatory response.In this study, we investigated the concentration of sevoflurane, which can induce postoperative cognitive dysfunction of aged rats with tibial fracture fixation, and further explore the role of glial cell activation in sevoflurane-related POCD, thought to explore appropriate anesthesia depth, and provide more theoretical basis for reducing the incidence of postoperative cognitive dysfunction in clinical.Part one: The effect of sevoflurane anesthesia with different concentration on cognitive function after surgery for aged ratObjective:To screen the concentration of sevoflurane that may induce postoperative cognitive dysfunction in aged rats.Methods:Ninety-six male Wistar rats weighing600～650g were randomly divided into6groups (n=16each):control group (group C), propofol group (group P), propofol+operation group (group PS),2.4%sevoflurane+operation group (group S1),3.1%sevoflurane+operation group (group S2),3.6%sevoflurane+operation group (group S3). Group C, P and PS inhaled30%O2-air for2h, group S1, S2and S3inhaled2.4%,3.1%and3.6%sevoflurane for2h, respectively. Group P, PS received propofol (0.5～0.7mg～kg-1·min-1) through caudal vein for2h, and the rest groups received normal saline at the same speed. During this time, group PS, S1, S2and S3received tibial fracture with pinning. On day1,3and7after surgery eight rats of each group were chosen to assess the cognitive function by Y-maze spatial recognition test, fear conditioning test and weight loss test, respectively, by which to screen the sevoflurane concentration group (group SS) that could induce postoperative cognitive dysfunction in aged rats.Results: Compared with group C, there was no statistically difference of freezing time percentage for groups in various training stages of training period (P>0.05), the number of arm visits, the duration of novel arm visits, the contextual percent freezing time and the cued percent freezing time were decreased on day1,3and7of group PS, S1, S2and S3(P<0.05), the weight had also declined and group S3was the most one; Compared with group PS, the number of arm visits and the duration of novel arm visits were decreased on day1and3, the contextual percent freezing time was declined on day1and the cued percent freezing time was decreased on day1,3and7of group S3(P<0.05).Conclusion:Sevoflurane anesthesia of high concentration (3.6%,1.5MAC) can induce postoperative cognitive dysfunction for aged rats.Part two:The role of glia activation at hippocampus in sevoflurane-related postoperative cognitive dysfunction for aged ratsObjective: To investigate the role of glia activation at hippocampus of sevoflurane-related postoperative cognitive dysfunction for aged rats.Methods: One hundred and forty four Wistar rats weighing600～650g were randomly divided into4groups (n=36each): control group (group C), propofol group (group P), propofol+operation group (group PS), and3.6%sevoflurane+operation group (group SS). Six rats of each group were chosen on days1,3and7after surgery to detect the morphology and the expression of CD68and GFAP of microglia and astrocytes in hippocampus by immunofluorescence, and the expression of IL-1β, IL-6and TNF-α by western blot.Results:Compared with group C, the expression of CD68, GFAP, IL-1β, IL-6and TNF-α were decreased on day1,3and7of group PS and SS (P<0.05). Compared with group PS, the expression of CD68, GFAP, IL-1β, IL-6and TNF-α were decreased on day1and3(P<0.05). The morphology of microglia and astrocytes of group PS and SS had changed.Conclusion: The mechanism of sevoflurane-related cognitive dysfunction may be involved with the enhancement for the activation of hippocampal glia cells. |
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