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Objective:To evaluate the role of miR-146a in hippocampal inflammatory responses in postoperative cognitive dysfunction (POCD) in mice.Methods:One hundred and sixty clean-grade male C57BL/6 mice, aged 12-16 weeks, weighing 22-28 g, were divided into 5 groups ( n=32 each) using a random number table method: control group (group C), group POCD, miR-146a agomir group (group Ag), miR-146a antagomir group (group At) and negative control group (group NC). The mice were subjected to an intramedullary fixation for tibial fracture under 1.5% isoflurane anesthesia to establish POCD model.At 2 days before operation, miR-146a agomir 0.5 nmol (0.1 nmol/μl) was injected into bilateral hippocampi in group Ag, miR-146a antagomir 2.5 nmol (0.5 nmol/μl) was injected in group At, miR-146a negative control solution 2.5 nmol (0.5 nmol/μl) was given in group NC, and the animals in group C did not receive any treatment.At 1 day before operation and at 1, 3 and 7 days after operation, open-field test was performed to evaluate spontaneous motor activity, and contextual fear conditioning test was performed to evaluate cognitive ability 15 min later.At 1 and 3 days after operation, the animals were sacrificed and hippocampi was removed for determination of expression of CD11b (a marker for activation of microglia) in hippocampal CA1 region by immunofluorescence staining.At 6, 12 and 24 h after operation, the expression of miR-146a was detected by quantitative real-time polymerase chain reaction, the expression of interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B p65 (NF-κB p65) and tumor necrosis factor-alpha (TNF-α) was determined by Western blot and interleukin-1beta (IL-1β) and IL-6 contents were determined by enzyme-linked immunosorbent assay. Results:There was no significant difference in the total exploring distance in the open-field test or percentage of freezing time in tone-fear conditioning test at each time point among the five groups( P>0.05). Compared with group C, the percentage of freezing time in the contextual fear conditioning test was significantly decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery and expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α were up-regulated and the contents of IL-1 β and IL-6 were increased at 6, 12 and 24 h after operation in group POCD ( P<0.05). Compared with group NC, the percentage of freezing time in the contextual fear conditioning test was significantly increased at 1, 3 and 7 days after operation, and the expression of CD11b was down-regulated at 1 and 3 days after surgery, and the expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α was up-regulated and IL-1β and IL-6 contents were decreased at 6, 12 and 24 h after operation in group Ag, and the percentage of freezing time in the contextual fear conditioning test was decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery was up-regulated, the expression of miR-146a was down-regulated and IRAK1, TRAF6, NF-κB p65 expression was up-regulated at 6, 12 and 24 h after operation, TNF-α expression was up-regulated and IL-1β and IL-6 contents were increased at 12 and 24 h after operation in group At ( P<0.05). Conclusion:miR-146a is involved in the process of hippocampal inflammatory responses, and the mechanism may be related to the inhibition of IRAK1-TRAF6-NF-κB signaling pathway in mice.
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Objective:To evaluate the changes in the blood-cerebrospinal fluid barrier in postoperative delirium rats.Methods:One hundred and forty-seven healthy female Sprague-Dawley rats, aged 3 months, weighing 240-300 g, were divided into 3 groups ( n=49 each) using a random number table method: control group (group C), anesthesia group (group A) and postoperative delirium group (group P). Group C received no treatment.Group A received 2-h anesthesia with 1.4% isoflurane.Group S underwent an exploratory laparotomy under 1.4% isoflurane anesthesia.The behaviors of rats in each group were tested at 24 h before surgery and 6, 9 and 24 h after surgery using buried food test, open field test and Y maze test.Sodium fluorescence was injected through the tail vein at 6, 9 and 24 h after surgery.Then the rats were sacrificed, the choroid plexus (CP) was obtained, and cerebrospinal fluid (CSF) of bilateral cerebral ventricles was collected, and the expression of ZO-1, occludin, claudin1, E-cadherin and VE-cadherin in CP was detected using Western blot.FITC-dextran 10, 40 and 70 kDa was injected through the tail vein at 6 h after surgery, and then CSF was collected for determination of the concentrations of NaFI, 10, 40 and 70 kDa fluorescein isothiocyanate labeled dextran (FITC-dextran) in CSF by fluorescence spectrophotometry.CP was obtained to observe the morphology of choroid plexus epithelial cells (CPECs) of bilateral cerebral ventricles with a transmission electron microscope. Results:Compared with group C and group A, the latency to eat food in buried food test was significantly prolonged, the time of staying at the central region was shortened, the percentage of the number of entries into novel arm and percentage of time of staying at novel arm in Y maze test were decreased, the freezing time in open field test was shortened, the expression of ZO-1, occludin and claudin1 in CP was down-regulated, the concentrations of NaFI and 10 kDa and 40 kDa FITC-dextranin CSF were increased ( P<0.05 or 0.01), the CPECs arranged at random and loose, the microvilli of CPECs were absent, the tight junction was blurred, and the gap became wider in group P. Conclusion:The occurrence of postoperative delirium is related to the change in blood-cerebrospinal fluid barrier.
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Objective To evaluate the relationship between mechanical ventilation-induced apoptosis in hippocampal neurons and mammalian taget of rapamycin ( mTOR) signaling pathway in mice. Methods Fifty healthy male C57BL∕6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=25 each) using a random number table method: control group ( group C ) and mechanical ventilation group ( group V) . The mice breathed spontaneously for 6 h in group C, and the mice were mechanically ventilated for 6 h in group V. Open field test and contextual fear conditioning test were conducted at 1 and 3 days after the end of ventilation. Hippocampal tissues were obtained at 1 day after the end of ventilation for determina-tion of the expression of mTOR, phosphorylated mTOR (p-mTOR), microtubule-associated protein 1 light chain 3Ⅱ( by Western blot) and apoptosis in hippocampal neurons ( by TUNEL) . The p-mTOR∕mTOR ratio and apoptosis index were calculated. Results Compared with group C, the time animals spent in the central square was significantly prolonged, the number of crossing the grid was reduced, the percentage of freezing time was decreased, the expression of microtubule-associated protein 1 light chain 3Ⅱwas up-regulated, and the p-mTOR∕mTOR ratio and apoptosis index were increased in group V ( P<0. 05) . Conclusion The mech-anism by which mechanical ventilation induces apoptosis in hippocampal neurons may be related to activation of mTOR signaling pathway in mice.
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Objective To compare the scalp nerve block versus local infiltration of incision for in-tracranial aneurysm clipping under general anesthesia. Methods Fifty-seven American Society of Anesthe-siologists physical statusⅠorⅡpatients of both sexes, aged 18-64 yr, scheduled for elective intracranial aneurysm clipping under general anesthesia, were divided into 3 groups ( n=19 each) using a random num-ber table method:control group ( group C) , scalp nerve block group ( group S) and local infiltration of in-cision group ( group I) . Anesthesia was induced by intravenously injecting propofol, sufentanil and cisatra-curium. Bilateral supraorbital nerve (2 ml), supratrochlear nerve (2 ml), zygomaticotemporal nerve (2 ml), auriculotemporal nerve (2 ml), greater occipital nerve (3 ml), lesser occipital nerve (3 ml) and the third occipital nerve ( 1 ml) blocks were performed with 0. 75％ ropivacaine after tracheal intubation in group B. Local infiltration of incision was carried out with 0. 75％ ropivacaine 15 ml in group I. Anesthesia was maintained by intravenously infusing propofol and remifentanil to maintain bispectral index value at 40-60. The fluctuation range of mean arterial pressure and heart rate was not more than 20％ of the baseline, and vasoactive agents were administered when necessary. Oxycodone 0. 1 mg∕kg was intravenously injected at 30 min before the end of surgery to perform preemptive analgesia. When visual analogue scale score>3 with-in 48 h after surgery, oxycodone 2 mg was intravenously injected as rescue analgesic, and administration was repeated when necessary ( at an interval>15 min) . The intraoperative consumption of propofol, remifen-tanil and vasoactive agents was recorded. Arterial blood samples were collected before anesthesia induction and at 3, 12, 24, 48 and 72 h after surgery for determination of serum interleukin-6 ( IL-6) , IL-10 and C-reactive protein ( CRP ) concentrations by enzyme-linked immunosorbent assay. The time of the first postoperative requirement for oxycodone and consumption of oxycodone within 48 h after surgery were recor-ded. The development of adverse reactions such as postoperative fever, nausea and vomiting, dizziness, respiratory depression, pruritus, local anesthetic intoxication, subcutaneous hematoma, and scalp infec-tion was also recorded. Results Compared with group C, the intraoperative consumption of remifentanil and requirement for nicardipine were significantly decreased, the concentration of serum IL-6 was decreased at 3 h after surgery, the concentration of serum CRP was decreased at 12 h after surgery, the concentration of serum IL-10 was increased at 12 and 24 h after surgery, the time of the first postoperative requirement for rescue analgesia was prolonged, the consumption of oxycodone was reduced, and the incidence of nausea and vomiting was decreased in group B, and the intraoperative consumption of remifentanil was significantly reduced in group I (P<0. 05). Compared with group I, the intraoperative consumption of remifentanil was significantly reduced, the requirement for nicardipine was decreased, the concentration of serum IL-6 was decreased at 3 h after surger-y, the concentration of serum CRP was decreased at 12 h after surgery, the concentration of serum IL-10 was in-creased at 12 and 24 h after surgery, the time of the first postoperative requirement for rescue analgesia was pro-longed, the consumption of oxycodone was reduced, and the incidence of nausea and vomiting was decreased in group B (P<0. 05). Conclusion Compared with local infiltration of incision, scalp nerve block is helpful in carrying out anesthetic model of low-consumption opioids and in maintaining intraoperative hemodynamics stable and is more helpful in inhibiting perioperative inflammatory and pain responses when used for the patients under-going intracranial aneurysm clipping under general anesthesia.
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Objective To evaluate the effects of sevoflurane on hippocampal neurogenesis in den-tate gyrus (DG) of mice of different ages. Methods Ninety-six SPF healthy male C57BL∕6 mice, aged 2 weeks, 6 weeks, 9 months and 20 months (24 mice for each age, 12 mice for each group), were divided into 2 groups (n＝48 each) using a random number table method: control group (group C) and sevoflurane group (group S). Group S inhaled 3. 0% sevoflurane for 2 h once a day for 3 consecutive days, while group C inhaled the mixture of air and O2. Six mice of each age were selected, and 5′-bromo-2′-deoxyuridine (BrdU) 50 mg∕kg was intraperitoneally injected immediately before and after inhalation once a day for 3 consecutive days in two groups. Mice were sacrificed at 24 h after the last inhalation (T1), brains were re-moved and hippocampi isolated for determination of the number of nestin and doublecortin ( DCX) positive cells in DG by immunohistochemistry. Mice were sacrificed at 4 weeks after the last inhalation ( T2), brains were removed and hippocampi isolated for determination of the number of neuronal nuclei antigen (NeuN)∕BrdU and glial fibrillary acid protein ( GFAP )∕BrdU positive cells by immunofluorescence. Re-sults Compared with group C, the number of nestin and DCX positive cells was significantly reduced at T1, and the number of NeuN∕BrdU and GFAP∕BrdU positive cells was reduced at T2in mice of 2 weeks and 20 months old (P＜0. 05), and no significant change was found in the indices mentioned above in mice of 6 weeks and 9 months old in group S ( P＞0. 05). Conclusion Three percent sevoflurane can inhibit hipp-ocampal neurogenesis in DG of immature and old mice and exerts no influence on hippocampal neurogenesis in DG of juvenile and adult mice.
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Objective To investigate the role of hippocampal cannabinoid receptor 2 (CB2R) in postoperative cognitive dysfunction (POCD) in mice.Methods Fifty-four healthy male C57BL/6 mice,aged 12-16 weeks,weighing 20-30 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),group POCD and POCD plus CB2R agonist JWH133 group (group POCD+J).The mice were subjected to an intramedullary fixation for tibial fracture under 1.5％ isoflurane anesthesia to establish POCD model.In group POCD+J,2 mg/kg JWH133 was injected intraperitoneally at a total volume of 10 ml/kg after emergence from anesthesia and then the injection was repeated once a day until the 7th day after surgery.Open field test was carried out on 1 day before surgery and 1,3 and 7 days after surgery to evaluate the locomotor activity.Fear conditioning test was carried out at 15 min after completion of open field test.Mice were sacrificed at 2 h after the end of behavioral test,and the hippocampus was harvested for determination of the expression of tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β),monocyte chemotactic protein-1 (MCP-1) and CB2R (by Western blot) and expression of CD11b in hippocampal tissues (by immunofluorescence).Results There was no significant difference in the total exploring distance in open field test,percentage of freezing time in contextual fear conditioning test or percentage of freezing time in tone-fear conditioning text at each time point among the three groups (P＞0.05).Compared with group C,the percentage of freezing time in contextual fear conditioning test was significantly decreased,and the expression of TNF-α,IL-1β,MCP-1,CD11b and CB2R was up-regulated after surgery in group S (P＜0.05).Compared with group S,the percentage of freezing time in contextual fear conditioning test was significantly increased,and the expression of TNF-α,IL-1β,MCP-1,CD11band CB2R was down-regulated after surgery in group S+J (P＜ 0.05).Conclusion Activation of hippocampal CB2R may be involved in the endogenous protective mechanism of POCD in mice,and the mechanism is related to inhibiting activation of hippocampal microglia and attenuating central inflammatory responses.
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Objective To evaluate the effect of exogenous miR-181b on postoperative cognitive dysfunction ( POCD) in mice. Methods A total of 108 clean-grade healthy male C57BL∕6 mice, weighing 25-30 g, were divided into 4 groups ( n=27 each) using a random number table method: control group ( group C) , POCD group, miR-181b agonist agomir group ( group Ag) , and agomir negative control group ( group AC) . POCD was induced by open tibial fracture in 2. 1％ isoflurane-anesthetized mice. A total vol-ume of miR-181b agomir 4μl ( 0. 25 nmol∕μl) was injected into bilateral hippocampi at 2 days before estab-lishing the model in group Ag. Agomir negative control solution 4μl was given at 2 days before establishing the model in group AC. Eighteen mice were selected at days 1, 3 and 7 after surgery, and contextual fear conditioning test was performed to assess cognitive function. Nine mice in each group were sacrificed at 6, 12 and 24 h after surgery ( 3 mice at each time point) , and the hippocampus was isolated for determination of miR-181b expression ( by quantitative real-time polymerase chain reaction) and interleukin-1β ( IL-1β) and tumor necrosis factor-α ( TNF-α) contents ( by enzyme-linked immunosorbent assay) . Results Com-pared with group C, the percentage of time spent freezing in the contextual fear conditioning test was signifi-cantly decreased at 1, 3 and 7 days after surgery, and the expression of miR-181b was down-regulated and the contents of IL-1β and TNF-α were increased at 6, 12 and 24 h after surgery in POCD and AC groups( P<0. 05) . Compared with POCD and AC groups, the percentage of time spent freezing in the contextual fear conditioning test was significantly increased 1, 3 and 7 days after surgery, and the expression of miR-181b was up-regulated and the contents of IL-1βand TNF-αwere decreased at 6, 12 and 24 h after surgery in group Ag ( P<0. 05). Conclusion Exogenous miR-181b can mitigate POCD, and the mechanism may be related to inhibiting inflammatory responses in the hippocampus of mice.
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Objective To investigate the changes of miR-146a expression in serum,hippocam-pus and prefrontal cortex in postoperative cognitive dysfunction (POCD) mice.Methods Fifty healthy male C57BL/6 mice,aged 12-14 weeks,weighing 25-30 g,were randomly divided into two groups (n =25 each)using a random number table:control group (group C)and anesthesia plus sur-gery group (group AS).Mice in group AS underwent open tibial fracture of the left hind paw with in-tramedullary fixation in aseptic conditions under general anesthesia with 2.1% isoflurne.Ten mice in each group received the fear conditioning test (FCT)on the 1,3 and 7 days after anesthesia/surgery. The rest of mice were sacrificed 24 h before (baseline),and 6,12,24,48 h after anesthesia/surgery, and then the serum,prefrontal cortex and hippocampus were collected or removed for detection of the expression of miR-146a using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results Compared with group C,the percentage of freezing time in contextual FCT was sig-nificantly decreased (P <0.05)in group AS,while no significant change in freezing time percentage was found in tone-cued FCT.In serum,compared with group C,miR-146a expression at 6,12,24, 48 h after anesthesia/surgery was significantly up-regulated in group AS (P < 0.05 );and in group AS,the expression of miR-146a was significantly decreased 6,24,48 h as compared to that at 12 h after anesthesia/surgery (P <0.05).In hippocampus,compared with group C,miR-146a expression at 6,12,24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a at 6,48 h after surgery was significantly decreased as compared to that at 12 h after anesthesia/surgery (P <0.05).In prefrontal cortex,compared with group C,miR-146a expression at 24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a was significantly increased at 48 h as compared to that at 24 h after anesthesia/surgery (P <0.05).Conclusion The expression of miR-146a in serum,hippocam-pus and prefrontal cortex in POCD mice was up-regulated,and changes of miR-146a expression may be related to the development of POCD.
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Objective To evaluate the effects of sevoflurane on neurogenesis in hippocampal den-tate gyrus(DG)of mice with Alzheimer′s disease. Methods Thirty-six SPF male APP∕PS1 mice, aged 8 months, weighing 30-35 g, were divided into 3 groups(n=12 each)using a random number table:Alzheimer′s disease group(group AD), oxygen group(group O2)and sevoflurane group(group Sev). Another 12 wild-type mice served as control group(group C). In group Sev, 30% sevoflurane was in-haled for 2 h once a day for 3 consecutive days. The mixture of air and oxygen was inhaled in group O2. Morris water maze test was performed on 22 to 28 days after the last sevoflurane inhalation. Then the mice were sacrificed and hippocampi were isolated for determination of doublecortin(DCX)positive cell count (by immunohistochemistry)and neuronal nuclei(NeuN)∕5-bromo-2′-deoxyuridine(BrdU)and glial fi-brillary acidic protein(GFAP)∕BrdU positive cell count in hippocampal DG(by immunofluorescence). Results Compared with group C, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in AD, O2and Sev groups(P<005). There was no significant difference in each parameter between group O2and group AD(P>005). Compared with group O2, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in group Sev(P<005). Conclusion Sevoflurane leads to cognitive decline through depressing neurogenesis in hippocampal DG of mice with Alzheimer′s disease.
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Objective To evaluate the relationship between the levels of microRNA-125b (miR-125b) and miR-181c in cerebrospinal flnid (CSF) before joint replacement and postoperative delirium (POD) in elderly patients.Methods Fifty-two patients of hoth sexes,aged ≥ 65 yr,weighing 45-70 kg,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elcctive hip or knee replacement under spinal anesthesia,were included in the study.CSF was collected after successful puncture to measure the levels of miR-181c and miR-125b by fluorescent quantitative real-time polymerase chain reaction.The patients were divided into POD group and non-POD group using the Chinese reversion of Confusion Assessment Method on postoperative days 1 and 2.Results The incidence of POD was about 28％ in the patients underwent hip or knee replacement.Compared with non-POD group,the preoperative level of miR-181c in CSF was significantly increased (P＜0.05),and no significant change was found in the preoperative level of miR-125b in CSF in POD group (P＞0.05).Conclusion The level of miR-181c in CSF before joint replacement is related to POD in elderly patients,and the preoperative level of miR-181c in CSF is a risk factor for POD.
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Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilation-induced activation of microglias in the hippocampi of mice.Methods Forty-two healthy male TLR4 gene knocked out C57BL/10ScNJNju mice and 42 wild type C57BL/6 mice,aged 10-12 weeks,weighing 20-25 g,were used in the study.The mice of either group were divided into 2 subgroups (n =21 each) using a random number table:spontaneous breathing subgroup (subgroup SB) and mechanical ventilation subgroup (subgroup MV).In subgroup SB,the mice were exposed to isoflurane for 6 h in an anesthesia chamber.After tracheal intubation,the mice were mechanically ventilated for 6 h when anesthesia was maintained with isoflurane in subgroup MV.Twelve mice were selected from each subgroup at 1 and 3 days after ventilation,fear conditioning test was performed to assess the cognitive function,and the rate of freezing time was recorded.Three mice in each subgroup were sacrificed at 1 day after ventilation,and the brains were removed to observe the morphological changes of microglias (by double immunofluorescent staining) and to count CD11b positive cells and co-expression of TLR4 with CD11b (TLR4/CD11b) positive cells in hippocampal microglias.Six mice in each subgroup were sacrificed at 1 day after ventilation,and the hippocampi were isolated for determination of the content of tumor necrosis factor-alpha (TNF-α) in hippocampal tissues by enzyme-linked immunosorbent assay.Results Compared with subgroup SB of wild type group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and TLR4/CD1 1b positive cells were increased,and the content of TNF-α was increased in subgroup MV of wild type group (P＜0.05),and the number of CD1 1b positive cells and content of TNF-α were significantly increased in subgroup MV of geue knockout group (P＜0.05).Compared with subgroup SB of gene knockout group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and content of TNF-α were increased in subgroup MV of gene knockout group (P＜0.05).Compared with subgroup MV of wild type group,the rate of freezing time was significantly increased at 1 and 3 days after ventilation,and the number of CD11b positive cells and content of TNF-α were decreased in subgroup MV of gene knockout group (P＜0.05).Conclusion The mechanism by which mechanical ventilation induces activation of microglias in hippocampi is partially related to TLR4 in mice.
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Objective To investigate the effect of parecoxib on hippocompal inflammation following partial hepatectomy in aged rats.The effects of selective COX-2 inhibitor (parecoxib) on hippocampal inflammation were also evaluated.Methods Seventy male rats,aged 20 months,weighing 500-600 g,were randomly divided into three groups: control (n=10),surgery (n=30),and parecoxib (n=30).Control animals received sterile saline to control for the effects of injection stress.Rats in the surgery group received partial hepatectomy under isoflurane anesthesia and sterile saline injection.Rats in the parecoxib group received surgery and anesthesia similar to surgery group rats,and parecoxib treatment.On postanesthetic day 1,3 and 7,animals were euthanized to assess the hippocampal COX-2 expression,PGE2 production and caspase-3 expression.Results Surgery significantly increased the expression of COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on day 1 postoperatively (P<0.01),until day 3 (P<0.05) compared to control group.Parecoxib treatment group significantly suppressed COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on postoperative day 1 and day 3 (P<0.05 or P<0.01),in comparison with the surgery group.There was no significant difference between control group and other groups of the expression of COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on day 7.Conclusion Partial hepatectomy induces a short-term hippocampal inflammatory response in the rats.Parecoxib suppressed the hippocampal inflammation via the down-regulation of COX-2 mRNA and protein,PGE2 and caspase-3 protein in rats following partial hepatectomy.
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Objective To investigate the risk factors for early postoperative cognitive function in the patients with peritoneal surface malignancies after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy(CRS-HIPEC).Methods Fifty-one patients(21 men and 30 women), ranged from 25 to 65 years,42-80 kg,ASA Ⅰ-Ⅲ,undergoing CRS-HIPEC under combined intrave-nous-inhalational anesthesia,were studied.Patients were assigned into postoperative cognitive dys-function (POCD)group or non-POCD group according to their performances of visual verbal learning test,concept shifting task,letter-digit coding test and stroop color-word test 1 day before operation and 7 days after operation.Years of education,medical history,duration of operation,intraoperative blood loss,frequency of cardiovascular events,amount of fluid infused per hour and VAS scores were recorded.Venous blood samples were taken at five time points:before surgery(T0 ),30 minutes after the beginning of the procedure(T1 ),30 minutes after the beginning of HIPEC(T2 ),at the end of the surgery(T3 )and 24 hours after the surgery(T4 ),to determine the concentration of serum amyloid A (SAA).pH,PaCO 2, Hb,blood glucose were recorded at T0-T2.Then the data was statistically analyzed.Results According to the diagnostic criteria,twenty patients developed POCD 20 (39.2%). There were significant differences between POCD and non-POCD groups on age,gender, pre-operative complications and the origin of tumor(P <0.05).The concentration of SAA increased from T2 and reached the peak at T4 ,and SAA concentration for patients in POCD group was higher than that for patients in non-POCD group(P <0.05).Compared with non-POCD group,the levels of blood glucose were significantly increased in POCD group at T2 (P <0.05).Conclusion CRS-HIPEC resul-ted in exaggerated and prolonged inflammatory response.Advanced age,female,diabetes,hyperten-sion,peritoneal carcinomatosis from ovarian cancer and endometrial cancer are associated with early POCD in the patients undergoing CRS-HIPEC.
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Objective To evaluate the effect of long?time mechanical ventilation on early postoper?ative inflammatory responses in the hippocampi of mice. Methods Forty?eight healthy male C57BL∕6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 3 groups ( n=16 each) using a random number table: control group ( group C) , operation group ( group O) and long?time mechanical ventilation after operation group ( group MV) . Open reduction and internal fixation was performed after tibial fracture was induced in O and MV groups. Group O inhaled isoflurane for 6 h after operation. The mice were me?chanically ventilated for 6 h under isoflurane anesthesia in group MV. On 1 and 3 days after the end of ven?tilation, 8 mice were randomly selected, and contextual fear conditioning test was carried out to assess the cognitive function. The rate of time spent freezing was calculated. Then venous blood samples were collected and hippocampi removed for determination of the levels of interleukin?6 ( IL?6) , tumor necrosis factor?al?pha ( TNF?α) and IL?1β in plasma and hippocampal tissues by enzyme?linked immunosorbent assay. Re?sults Compared with group C, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group O ( P<0.01) . Compared with group O, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group MV ( P<0.01) . Conclusion The mechanism by which long?time mechanical ventilation leads to early postoperative cognitive dysfunction is related to induction of in?flammatory responses in the hippocampi of mice.
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Objective To evaluate the effect of intraperitoneal hyperthermic chemotherapy ( IPHC) on postoperative delirium in the patients undergoing cytoreductive surgery ( CS) . Methods One hundred twenty patients of both sexes, aged 18-64 yr, weighing 40-70 kg, of ASA physical status Ⅰ-Ⅲ, scheduled for elective CS under general anesthesia, were enrolled in the study. According to whether or not the patients underwent IPHC, they were divided into 3 groups ( n=40 each): CS group, IPHC 1 h group (group IPHC1) and IPHC 2 h group (group IPHC2). IPHC1 and IPHC2 groups were perfused with chemotherapeutics for 1 and 2 h, respectively, after CS. Postoperative delirium was evaluated using the Confusion Assessment Method for the Intensive Care Unit at 1-3 days after surgery. Results The incidence of postoperative delirium was 15%, 28% and 38% in CS, IPHC1 and IPHC2 groups, respectively. The incidence of postoperative delirium was significantly higher in IPHC1 and IPHC2 groups than in group CS, and in group IPHC2 than in group IPHC1. Conclusion IPHC may increase the development of postoperative delirium in the patients undergoing CS.
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Objective To evaluate the effect of mechanical ventilation on synaptic plasticity in hippocampal CA1 region of mice.Methods Thirty-six male C57BL/6 mice,aged 8-10 weeks,weighing 20-25 g,were randomly divided into 2 groups (n =18 each) using a random number table:control group (group C) and mechanical ventilation group (group M).After anesthesia,endotracheal intubation was carried out,and open reduction and internal fixation was performed after tibial fracture was induced in mice.In C group,the endotracheal tube was removed after operation,and then the mice were exposed to 1.5％ isoflurane for 6 h in a chamber.In M group,the mice were mechanically ventilated continuously for 6 h,and 1.5％ isoflurane was inhaled to maintain the level of anesthesia.At 2 h and 1 and 3 days after the end of ventilation,6 mice were chosen from each group,and fear conditioning test was performed,and the percentage of freezing time was recorded.Six mice were chosen from each group on 1 day after the end of ventilation,and novel object recognition task was carried out.The preference index was calculated at 5-min,2-h and 1-day intervals on 4 days after the end of ventilation.Three mice were chosen from each group on 1 day after the end of ventilation and sacrificed,and the hippocampi were isolated for examination of hippocampal ultrastructure (with electron microscope) and for calculation of the number of synapses.Three mice were chosen from each group on 1 day after the end of ventilation and sacrificed,and the whole brain was removed for measurement of dendritic spine density in brain tissues.Results Compared with group C,the percentage of freezing time was significantly decreased at 2 h and 1 day after operation,the preference index at different intervals was decreased,the number of synapses in hippocampal CA1 region was reduced,and the apical and basal dendritic spine densities were decreased in group M.Conclusion Mechanical ventilation can change synaptic plasticity in hippocampal CA1 region of mice.
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Objective To evaluate the role of endothelial nitric oxide synthase (eNOS) in inflammatory responses in mice with ventilator-induced lung injury using gene knockout.Methods Twenty-four male C578L/6J wild type mice and 24 male B6.129P2-Nos3tm1Unc/NJU (eNOS gene knockout) mice,aged 10-12 months,weighing 20-25 g,were randomly assigned into 2 groups (n=12 each) using a random number table:sham operation group (group S) and mechanical ventilation group (group MV).The animals were anesthetized with intraperitoneal 1％ pentobarbital sodium 70 mg/kg,and mechanically ventilated after tracheal intubation.The animals were mechanically ventilated for 4 h (oxygen flow rate 0.5 L/min,FiO2 50％,VT 15 ml/kg,RR 70 bpm,PEEP 2 cmH2O).After 4 h of ventilation,blood samples were obtained from the internal carotid artery for detection of PaO2.The animals were then sacrificed and the lungs were removed for determination of wet/dry lung weight (W/D) ratio,myeloperoxidase (MPO) activity,contents of malondialdehyde (MDA),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α),and pulmonary microvascular permeability,and for microscopic examination of the pathological changes of lung (with electron microscope).Results Compared with group S of wild type mice,PaO2 was significantly decreased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-oα and NO,and pulmonary microvascular permeability were increased in MV groups of wild type and gene knockout mice,and no significant change was found in the parameters mentioned above in group S of gene knockout mice.Compared with group MV of wild type mice,PaO2 was significantly increased,while W/D ratio,MPO activity,contents of MDA,IL-6,TNF-α and NO and pulmonary microvascular permeability were decreased in group MV of gene knockout mice.The pathological changes of lung were significantly attenuated in group MV of gene knockout mice as compared with group MV of wild type mice.Conclusion eNOS is involved in inflammatory responses in mice with ventilator-induced lung injury.
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Objective To investigate the adjuvant effect of intravenous immunoglobulin on patients with sepsis-associated thrombocytopenia. Methods A total of 229 patients with sepsis with platelet count less than 3 × 109/L, were included in this prospective, randomized, controlled study. The patients were divided into the intervening group and the control group. Conventional treatments were applied in the two both groups , while in the intervening group, intravenous immunoglobulin with a dose of 0.4 g/(kg·d) for 5 consecutive days was administered. The end-points were the platelet counts on day 1,day 3,day 5,and day 7 post-intravenous immunoglobulin, patients’ in-ICU time and the 28-day in-hospital mortality. Results Compared with the control group, the platelet count recovered dramatically after 5-day intravenous immunoglobulin in the intervening group. Moreover , the 28-day in-hospital mortality and in-ICU time were also dramatically improved in the intervening group. Conclusion Intravenous immunoglobulin can enhance the recovery of platelet counts , shorten the in-ICU time and reduce the hospital mortality in patients with sepsis- associated thrombocytopenia (PLT count < 30 × 109/L).
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Objective To investigate the effect of continuous venous-venous hemofiltration (CVVH) and continuous venous-venous hemodialysis (CVVHD) on patients with lactic acidosis.Methods A total of 137 cases with lactic acidosis were included in this prospective randomized control study.lhe patients were collected from the University of Hong Kong-shenzhen Hospitall and the First Affiliated Hospital of Shantou University Medical College from April 2009 to April 2013.Inclusion criteria were patients with lactic acidosis.Exclusion criteria were patients with end-stage malignancy or terminal stage of illnesses.The patients were randomly divided into two groups:CVVH group and CVVHD group,and patients of both group were intervened with conventional treatments as well.For each group,the lactic acid and blood gas analysis were tested before CRRT,and at 4 hours,8 hours,12 hours,24 hours,and 48 hours of CRRT.The patients' mortality and length of ICU stay time were analysed and recorded.Statistical analysis was performed using SPSS 15.0software.Results When the length of time for treatment was the same,the efficacy between CVVH group and CVVHD group showed no difference in blood lactic acid level [4 h:(11.65 ± 3.39) mmol/L vs.(11.12±2.65) mmol/L; 8 h:(8.78±2.35) mmol/L vs.(8.59±2.09) mmol/L; 12 h:(6.91 ±1.67)mmol/Lvs.(6.74±1.76) mmol/L;24h:(1.66±0.39) mmol/Lvs.(1.51±0.30) mmol/L; 48 h:(0.95 ±0.24) mmol/L vs.(0.66 ±0.20) mmol/L,P ＞ 0.05) and pH value [4 h:(6.93 ±0.14) vs.(7.05±0.09);8h:(7.04±0.10)vs.(7.12±0.05); 12h:(7.13±0.07)vs.(7.20±0.04);24h:(7.30±0.03) vs.(7.38±0.04); 48h:(7.41 ±0.03) vs.(7.46±0.02),P＞ 0.05].There are also no difference in the hospital mortality (11.4％ vs.10.4％,P=0.854) and length ofICU stay time [(9.5 ±2.4) d vs.(8.8 ± 2.9) d,P =0.329].Conclusions Both CVVH and CVVHD can effectively correct hyperlactemia,enhance acid-base balance,contributing no differences in length of ICU stay time and patients' hospital mortality.
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Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilationinduced increase in pulmonary capillary permeability in diabetic mice.Methods Two types of mice,aged 8-10 weeks,weighing 20-25 g,were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type (C3H/HeJ).Diabetes was induced by intraperitoneal streptozotocin 150 mg/kg (in citric acid buffer solution 0.1 mol/L) and confirmed by blood glucose level ＞ 16 mmol/L.Each type of diabetic mice was randomly divided into 2 groups (n =14 each):group diabetes + sham operation (group DS) and group diabetes + mechanical ventilation (group DM).The animals were anesthetized with intraperitoneal ketamine,midazolam and atropine.Tracheal intubation was performed and the animals kept spontaneous breathing in group DS.The animals were mechanically ventilated (FiO2 50％,RR 70 bpm,VT 15 ml/kg,PEEP 2 cmH2O) for 4 h in group DM.Arterial blood samples were obtained at 4 h of ventilation for blood gas analysis,PaO2 and PaCO2 were recorded,and NO concentration in the serum was measured.Then the animals were sacrificed and the lungs were removed for determination of W/D lung weight ratio (W/D ratio),content of evans blue (EB),and expression of caveolin-1,endothelial nitric oxide synthase (eNOS) and phosphor-eNOS (p-eNOS) (by Western blot).The ratio of p-eNOS/eNOS was calculated.Results Compared with group DS,PaO2,PaCO2 and p-eNOS/eNOS ratio were significantly decreased,and W/D ratio,EB content and caveolin-1 expression were increased in group DM (P ＜ 0.05).Compared with C3H/HeN mice,W/D ratio,caveolin-1 expression and EB content were significantly decreased,peNOS/eNOS ratio and serum NO concentrations were increased (P ＜ 0.05),and no significant changes in PaO2 and PaCO2 were found in C3H/HeJ mice in group DM (P ＞ 0.05).Conclusion TLR4 increases the pulmonary capillary permeability after mechanical ventilation in diabetic mice through effectively combining with caveolin-1 and reducing NO bioavailability.