The Effects And Mechanism Of Propofol On Microglial Activation And Postoperative Cognitive Function

Part Ⅰ Effects of propofol on microglial activation and its mechanismObjective To investigate the effects of propofol on microglial activation and its mechanism.Methods Microglial BV-2 cells were divided into control group、propofol group、lipopolysaccharide(LPS)group、LPS+propofol group、IL-4 group、IL-4+ propofol group、DMSO group.The control group cells were added with PBS;propofol group cells were added with propofol 30μM;LPS group cells were treated withl μg/mlLPS;LPS+propofol group cells were pretreated with 1 μg/ml LPS for 1h and then propofol 30 μM for 24h;IL-4 group cells were treated with 20ng/mL IL-4;IL-4+propofol group cells were prtreated with 20ng/mL IL-4 for 1h and then propofol 30 μM for 24h;DMSO group was treated with 0.1%DMSO as a solvent group.The morphological changes were obeserved and the levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-a(TNF-a),interleukin-4(IL-4),interleukin-10(IL-10),Arginase-1(Arg-1)in supernatants were measured by Enzyme-linked immunosorbent assay(ELISA),which can makesure the activated microglia model M1、M2 were set up and the cell viability was determined by MTT colorimetric assay to check the effect of propofol on the cell viability of activated microglial.Besides,the effect of propofol on unactivated microglial and activated microglial M1、M2 releasing cytokines were also measure.In addition,the expression of p38MAPK and TLR4、TRIP、JNK、ERKmRNA were detected by Reverse transcription-polymerase chain reaction(RT-PCR).The expression of p38MAPK and TLR4、TRIP、JNK、ERK protein were detected by Western blot.Results After treated with LPS and IL-4 respectively,the morphology of unactivated microglia changed to activated microglia.And the concentration of IL-1β,IL-6 and TNF-a in supernatant of LPS group were significant higher than control group;the levels of IL-4,IL-10,Arg-1 in IL-4 group were also significant higher than control group.Which meaned the model of activated microglial M1 and M2 were set.Besides,the cell viability of microglial in LPS group and LPS+propofol group were significant lower respectively than that in control group and propofol group(P<0.05).But the cell viability of IL-4+propofol group and IL-4 group were higher than IL-4 group and control group weakly.There was no significant difference among these groups.After treated with propofol for 24h,no significant difference were observed of propofol on unactived microglia.However,the levels of IL-1β,IL-6 and TNF-a in supernatant of LPS+propofol group were significant lower than those in LPS group(P<0.05).And In IL-4+propofol group,the levels of IL-4、IL-10、Arg-1 were a little bit higher than IL-4 group,but the differences were not significant.Similarly,The expression of p38MAPK、TLR4mRNA and protein in LPS group and LPS+propofol group were higher respectively than that in control group and propofol group(P<0.05).Meanwhile,the expression of p38MAPK and TLR4 mRNA and protein in LPS+propofol group were lower than that in LPS group(P<0.05).However,there were no significant difference of TRIP、JNK、ERK mRNA and Protein among these groups(P>0.05).Conclusion Propofol has the effect of inhibiting the hyperactivity and inflammatory response of microglial M1,and its mechanism may be related to the down-regulation of TLR4-p38MAPK signaling pathway.Part Ⅱ Effects of propofol on BIS index and postoperative cognitive function in elderly patients undergoing thoracolumbar surgeryObjective:To investigate the effects of propofol on bispectral index(BIS)and postoperative cognitive function in elderly patients undergoing thoracolumbar surgery.Methods:from July 2014 to March 2015,82 patients in our hospital were prepared to have thoracolumbar surgery.According to the random table,they were divided into observation group 41 cases and control group 41 cases randomly.During the operation,the control group was maintained by sevoflurane anesthesia,and the observation group was maintained by propofol anesthesia.The recovery time of spontaneous breathe,eye opening time,extubation time were recorded.MoCA score were measured before operation and 1 day after operation、3 days after operation,and then be compared between the two groups.The occurrence of 24h cognitive dysfunction and the change of BIS index before operation and during operation were also compared.Results:The recovery time of spontaneous breathe,eye opening time,extubation time in the propofol group were significant shorter than that in the sevoflurane group(P<0.05).The MoCA scores of postoperative 1 day in the two groups were all lower than that before operation(P<0.05).The MoCA scores of postoperative 3 days in the sevoflurane group were lower than that before operation(P<0.05).However,there were no significant differences of the MoCA score in the propofol group before operation and 3 days after operation(P>0.05);the MoCA score of propofol group after operation was higher than that in the sevoflurane group(P<0.05).The morbidity of postoperative cognitive dysfunction in the propofol group was less than that in the sevoflurane group(P<0.05).There was no significant difference in BIS index between the two groups(P>0.05).Conclusion:The effect of propofol on the recovery of senile thoracolumbar surgery patients were quick,the postoperative cognitive function was relatively small and had a clinical advantage.