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Objective To evaluate the effect of preoperative sleep deprivation on hippocampal Tolllike receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in aged mice with postoperative cognitive dysfunction.Methods Sixty clean-grade healthy male C57BL/6J mice,aged 16 months,weighing 28-36 g,were divided into 4 groups (n=15 each) using a random number table method:control group (group C),surgery group (group S),sleep deprivation group (group SD) and sleep deprivation plus surgery group (group SD+S).Mice were fed a common diet in group C.Mice were sleep-deprived for 24 h in group SD.Tibial fracture internal fixation was performed in group S.Tibial fracture internal fixation was performed after 24-h sleep deprivation in group SD+S.Cognitive function was assessed using the contextual fear conditioning test at days 3 and 7 after operation.The animals were sacrificed at day 7 after operation,brains were removed and hippocampi were isolated for determination of tumor necrosis factor-alpha (TNF-α) content (by enzyme-linked immunosorbent assay) and expression of TLR4 and p-NF-κB p65 (by Western blot).Results Compared with group C,the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation,the content of TNF-α was increased,and the expression of TLR4 and p-NF-κB p65 was up-regulated in S,SD and SD+S groups (P＜0.05).Compared with group S and group SD,the percentage of time spent freezing induced by condition and percentage of time spent freezing induced by context were significantly decreased at days 3 and 7 after operation,the content of TNF-α was increased,and the expression of TLR4 and p-NF-κB p65 was up-regulated in group SD+S (P＜0.05).Conclusion Preoperative sleep deprivation further accentuates postoperative cognitive dysfunction,and the mechanism is related to activating TLR4/NF-κB signaling pathway and inducing inflammatory responses of aged mice.
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Objective To investigate the protective effects of tanshinone-IIA sodium injection post-conditioning combined with controlled low central venous pressure on hepatic ischemia-reperfusion injury during liver resection.Methods Eighty patients scheduled for liver resection, 46 males and 34 females, aged 30-65 years, BMI 20-26 kg/m2, ASA physical status Ⅰ or Ⅱ, were randomly divided into four groups: tanshinone-IIA sodium post-conditioning (group D), tanshinone-IIAsodium post-conditioning combined with controlled low central venous pressure (CVP 1-5 cm H2O) group (group DL), controlled low central venous pressure (CVP 1-5 cm H2O) group (group L) and control group (group C) that took the static-compound anesthesia and maintained CVP 6-12 cm H2O, 20 cases in each group.The venous blood samples were drawn from internal carotid vein at different time point: pre-occlusion ten minutes (T0), post-occlusion 2 h (T1), 6 h (T2), 12 h (T3), 24 h after operation (T4), and then detected the levels of NF-κB, intercellular cell adhesion molecule-1 (ICAM-1), ALT and AST.The MAP was detected, HR and CVP were recorded.Results Compared with group C and group D, CVP were significantly lower at T0and T1in group L and group DL (P＜0.01).Compared with T0, levels of NF-κB, ICAM-1, ALT and AST in four group at T1-T4were significantly increased (P＜0.01).Compared with group C, levels of NF-κB, ICAM-1, ALT and AST in group DL, group L and group D at T1-T4 were significantly decreased (P＜0.05).Compared with group DL, levels of NF-κB, ICAM-1, ALT and AST in group D and group L at T1-T4 were significantly increased (P＜0.01).Conclusion Tanshinone-IIA sodium injection post-conditioning, combined with controlled low central venous pressure in patients with partial hepatectomy, can reduce the degree of ischemia-reperfusion injury.
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Objective To investigate the effects of different duration hypotension thresholds on p-Tau-181 and Aβ-42 protein expression and cognition in rats. Methods Thirty-nine healthy male SD rats were randomly di-vided into 4 groups:the control group(group C,n=9),the hypotension group(groupA1、A2、A3 ,n=10). The blood pressure of groupA1、A2、A3 was measured in different time of 2 h、4 h、6 h ,for 5 days. The antihyperten-sive group of mean arterial pressure(MAP)were maintained in the 50~55 mmHg safe range. Morris water maze was used to detect the spatial learning and memory ability of rats. The levels of Aβ42 and p-Tau-181 were detected by ELISA. Results There was no significant difference in mortality of rats in each group (P > 0.05). Compared with the group C,the escape latency and swimming distance of A2 group and A3 group were increased(P<0.05). In 3~7 days after operation,the cerebrospinal fluid P-Tau-181 and Aβ42 protein expression increased in the A2 group and A3 group compared with the A1 group(P<0.05). The escape latency and swimming distance of the A2 group and the A3 group were significantly longer than those in the control group. Aβ42 and p-Tau-181 were signifi-cantly increased in A3 group(P < 0.05). Compared with the A2 group,the increase of Aβ42 and p-Tau-181 in the A3 group was not significant(P<0.05). Conclusion Long-term controlled hypotension may lead to postoper-ative cognitive dysfunction which may relate to the increase of Aβ42 and p-Tau-181 protein expression.
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Objective To evaluate the role of Wnt/β-catenin signaling pathway in lithium chloride preconditioning-induced improvement in postoperative cognitive function of aged rats.Methods A total of 100 pathogen-free healthy male Sprague-Dawley rats,aged 18 months,weighing 540-650 g,were divided into 5 groups (n =20 each) using a random number table:control group (group C),surgery group (group S),lithium chloride preconditioning group (group L),secreted frizzled-related protein 1 (sFRP-1) group (group F) and lithium chloride preconditioning plus sFRP-1 group (group L+F).Lithium chloride 2 mmol/kg was intraperitoneally injected once a day for 5 consecutive days before operation in L and L+ F groups.In F and L + F groups,sFRP-1 10 μl (concentration 10 μg/ml) was injected into the ventricle at 1 day before operation.Ten rats in each group were randomly sacrificed at 1 day after operation,and the hippocampi were removed for determination of the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β),3-catenin and Wnt in hippocampal tissues (by Western blot).The rest rats underwent Morris water maze test at day 3-7 after operation,and the concentrations of amyloid beta 42 (A3-42) and phosphorylated tau-181 protein (p-tau-181) in cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay at day 7 after operation.Results Compared with group C,the escape latency was significantly prolonged at 3-7 days after operation,and the concentration of Aβ-42 in CSF was increased in the other four groups,and the expression of Wnt,p-GSK-3β and β-catenin in hippocampal tissues was down-regulated in group S,the expression of Wnt,p-GSK-3β and β-catenin in hippocampal tissues was significantly up-regulated in L and L+F groups,and the concentration of p-tau-181 in CSF was significantly increased in S and L+F groups (P＜0.05).Compared with group S,the escape latency was significantly shortened at 3-7 days after operation in group L and at 5-7 days after operation in group L+F,and the expression of Wnt,p-GSK-3β and β-catenin was significantly up-regulated,and the concentrations of Aβ-42 and p-tau-181 in CSF were decreased in L and L+F groups (P＜0.05).Compared with group L,the escape latency was significantly prolonged at 3-6 days after operation,the expression of Wnt,p-GSK-3β and β-catenin was down-regulated,and the concentration of p-tau-181 in CSF was increased in group L+F (P＜ 0.05).Compared with group F,the escape latency was significantly shortened at 3-7 days after operation,the expression of Wnt,p-GSK-3β and β-catenin was up-regulated,and the concentrations of Aβ-42 and ptau-181 in CSF were decreased in group L+F (P＜0.05).Conclusion The mechanism by which lithium chloride preconditioning improves in postoperative cognitive function is partially related to activating Wnt/β-catenin signaling pathway in aged rats.
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Objective: To investigate the effect of sevolfurane (SEVO) post-conditioning on protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway for protecting ischemia/reperfusion (I/R) injury in isolated rat’s heart. Methods: A total of 84 isolated rat’s heart prepared by Langendorff method were randomly divided into 7 groups andn=12 in each group.①Sham group,②I/R group,③SEVO post- conditioning (SPC) group,④NVP-BEZ235 solvent dimenthyl sulfoxide (DMSO) group,⑤Phosphatidyl inositol 3-kinase (PI3K)/mTOR dual inhibitor NVP-BEZ235 (BEZ) group,⑥BEZ+SPC group and⑦SEVO alone group. The hearts received 30 min ischemia followed by 120 min reperfusion with relevant treatment except for Sham group and SEVO group in which the hearts were without ischemia process. Myocardial infarct (MI) size and tissue pathological changes were observed, protein expressions of phosphor-AKT (P-AKT)/total-AKT, P-mTOR/total-mTOR, Beclin1, Bax/Bcl-2 and cleaved Caspase-3 were examined at the end of reperfusion respectively. Results: Compared with I/R group, SPC group presented decreased MI size (26.28±4.00) % vs (49.22±3.66) % and reduced tissue pathological changes; up-regulated protein expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 79.85% and 67.02%, while down-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 33.77%, 69.26% and 48.84%respectively, allP<0.05. Compared with SPC group, BEZ+SPC group sowed increased MI size (53.85±4.06) % vs (26.28±4.00) %and elevated tissue pathological changes; down-regulated proteins expressions of P-AKT/total-AKT and P-mTOR/total-mTOR by 46.06% and 42.95%, while up-regulated protein expressions of Beclin1, Bax/Bcl-2 and cleaved Caspase-3 by 29.90%, 206.85% and 114.65% respectively, allP<0.05. Conclusion: SPC may activate AKT/mTOR pathway and inhibit cardiomyocyte autophagy and apoptosis, thereby attenuate I/R injury in isolated rats’ heart.
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Objective To investigate the effects of Saikosaponin A (SSA)on cognitive function and cAMP/CREB signaling pathway and expression of BDNF in mice after traumatic brain injury. Methods Sixty SD male mice were randomized into three groups:shame operation group (group S, n =20),trauma group (group T,n =20)and SSA treatment group (group A,n =20).Mice received an administration of SSA 5 mg/kg (group A)or equal volume saline (group S,group T)immediately and once daily for 5 consecutive days after trauma.The cognitive function was detected by Morris wa-ter maze test on day 1,3,7 and 14 after trauma.The hippocampal tissues were harvested after be-havioral tests and homogenized for measuring the levels of brain derived neurophic factor (BDNF)and cyclic AMP (cAMP)by ELISA as well as the levels of cAMP-response element binding protein (CREB)and phosphorylation-cAMP-response element binding protein (pCREB)by western bolt. Results Compared with group S,the escape latency and swimming distance were significantly pro-longed in group T on day 1,3,7 and 14 and group A on day 1,3 after trauma (P <0.05 );while compared with group T,they were significantly shorter in group A on day 7,14 after trauma (P <0.05).Compared with group S,the levels of BDNF,cAMP,CREB and pCREB were significantly de-creased in group T(P < 0.05 ).Compared with group T,the levels of BDNF,cAMP,CREB and pCREB were significantly increased in group A (P <0.05).Conclusion SSA can significantly improve cognitive dysfunction in mice after traumatic brain injury,and the mechanism may be related to the activation of cAMP/CREB signaling pathway and up-regulation of BDNF.
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Objective To investigate the role of AKT/GSK3β/mTOR signaling molecule in myocardial protection of sevoflurane postconditioning.Methods Thirty-nine male Sprague-Dawley rats,weighing 200-250 g,installed in vivo myocardial ischemia-reperfusion model by left anterior de-scending coronary occlusion for 30 min.Rat hearts were randomly divided into 3 groups (n = 13 ):sham control group (group Sham),purely ischemia-reperfusion group (group IR),sevoflurane post-conditioning group (group SPC).With the exception of group Sham,each group was subjected to oc-clusion for 30 min followed by 2 h reperfusion.Group SPC was subjected to sevoflurane postcondi-tioning:2.4% sevoflurane was inhaled for 1 5 min starting from the end of ischemia until 1 5 min after beginning of reperfusion,while 33% oxygen was inhaled in the other groups.At the end of 2 h reper-fusion,cardiac function was evaluated by two-dimensional echocardiography,myocardial infarction size was measured by using 1% 2,3,5-triphenyltetrazolium chloride triazole (TTC),myocardial ultra-structural alterations was detected by transmission electron microscopy (TEM),cardiomyocytes ap-optosis was examined by terminal deoxynucleotidyl nickend labeling (TUNEL),the expressions of p-AKT/t-AKT, p-GSK3β/t-GSK3β, p-mTOR/t-mTOR,Bcl-2 and Bax proteins was measured by Western blot.Results Compared with group Sham,cardiac function was deteriorated,myocardial in-farct size was increased,cardiomyocyte mitochondrial damage was increased,positive apoptotic car-diomyocyte was increased,the expression of Bcl-2 was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bax were up-regluated in group IR (P <0.05).Compared with group IR,cardiac function was improved,myocardial infarct size was de-creased,cardiomyocyte mitochondrial damage was decreased,positive apoptotic cardiomyocyte was decreased,the expression of Bax was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bcl-2 were up-regluated in group SPC (P < 0.05 ). Conclusion Sevoflurane postconditioning can mitigate ischemia-reperfusion injury to in vivo rat hearts,decreased cardiomyocyte mitochondrial damage,inhibited cardiomyocyte apoptosis,and its mechanism was related to the activation of AKT/GSK3β/mTOR signaling molecule.
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Objective To explore the similarities and differences between finger photoplethysmogram (PPG) and CSI in monitoring the depth of anaesthesia in Chinese adults under general anaesthesia. Methods Ninety-three patients, ASA ⅠorⅡ, aged 20-67, under general anaesthesia were enrolled. Anaesthesia was induced with target-controlled infusion (TCI) of propofol. The initial TCI concentration of propofol was set at 0.5 mg·L-1 followed by increments of 0.5 mg·L-1 at 3-min interval until the score of Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS)reached 0. PPG and CSI were continuously monitored and their values were recorded every 2-4 seconds. MOAAS was recorded every 30 seconds to evaluate the sedation level in the study period. ResultsFor the periodfrom pre-induction to pre-intubation, the difference of photoplethysmogram amplitudevalues had statistical significance between level 4 and level 3, level 3 and level 2 of MOAAS (P<0.05). CSIvalues declined along with the decrease of MOAAS levels and were statistically different between every two neighboring levels of MOAAS (P < 0.05). Photoplethysmogram amplitude (PPGA) and pulse beat interval (PBI) values showed significant differences before and after intubation, pre- and post-incision (P < 0.05). Conclusions PPGA and PBI appear to be suitable to monitor the nociceptive component of balanced general anesthesia , while the CSI exhibits a good performance in monitoring the sedation or hypnotic component of balanced general anesthesia , thusthe combination of PPGA and CSI would benefit the monitoring of the adequacy of depth of anaesthesia.