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Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.
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Objective:To evaluate the role of ten-eleven translocation methylcytosine dioxygenase 3 (TET3) in trigeminal ganglion in maxillofacial inflammatory pain in mice.Methods:Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 19-23 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), inflammatory pain group (group IP), control+ TET3-siRNA group (group C+ siTET3), inflammatory pain+ TET3-siRNA group (group IP+ siTET3) and inflammatory pain+ negative control Scrambled-siRNA group (group IP+ siNC). Normal saline or complete Freund′s adjuvant (CFA) 10 μl was injected into the temporomandibular joint of mice, respectively, and the mechanical paw withdrawal threshold (MWT) was measured at 1, 4, 8 and 12 days after injection (T 1-4). Before injection of normal saline or CFA, 0.75 μl siTET3 or siNC was injected into the trigeminal ganglion and the animals were then sacrificed and trigeminal ganglion was removed at T 2 for determination of the expression of TET3 by Western blot in C+ siTET3, IP+ siTET3 and IP+ siNC groups. Results:Compared with group C, MWT was significantly decreased at T 1-3 , the expression of TET3 in trigeminal ganglion was up-regulate in group IP ( P<0.05 or 0.01). Compared with IP and IP+ siNC groups, MWT was significantly increased at T 2, 3, and the expression of TET3 in trigeminal ganglion was down-regulate in group IP+ siTET3 ( P<0.05 or 0.01). Conclusion:TET3 in trigeminal ganglion is involved in the development of maxillofacial inflammatory pain in mice.
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Objective:To evaluate the effect of dexmedetomidine on pyroptosis in rats with endotoxin-induced acute lung injury (ALI).Methods:Sixty SPF male Sprague-Dawley rats, aged 6 weeks, weighing 200-220 g, were divided into 5 groups ( n=10 each) by a random number table method: control group (group C), ALI group and different doses of dexmedetomidine groups (D 1-3 groups). In ALI group and D 1-3 groups, LPS 5 mg/kg was intraperitoneally injected to establish endotoxin-induced ALI model.Immediately after establishing the model, dexmedetomidine 12.5, 25.0 and 50.0 μg/kg were intraperitoneally injected in D 1-3 groups, and the equal volume of normal saline was intraperitoneally injected in group C, once a day for 14 consecutive days.After the end of administration, the rats were sacrificed, the left bronchus was lavaged, and the left bronchoalveolar lavage fluid (BALF) was collected for determination of the concentrations of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and the lung tissue was taken for determination of the wet/dry weight ratio (W/D ratio) and expression of cleaved-caspase-1, N-terminal of the spliceosome (GSDMD-N), IL-18 and IL-1β (by Western blot) and for microscopic examination of the pathological changes (with a light microscope). Results:Compared with group C, the W/D ratio of lung tissues was significantly increased, the concentrations of IL-1β, IL-6 and TNF-α in BALF were increased, the expression of cleaved-caspase-1, GSDMD-N, IL-1β and IL-18 in lung tissues was up-regulated ( P<0.05), and the pathological damage was aggravated in ALI group and D 1-3 groups.Compared with group ALI, the W/D ratio of lung tissues was significantly decreased, and the concentrations of IL-1β, IL-6 and TNF-α in BALF were decreased, the expression of cleaved-caspase-1, GSDMD-N, IL-1β and IL-18 in lung tissues was down-regulated in a dose-dependent manner ( P<0.05), and the pathological damage was significantly reduced in D 1-3 groups. Conclusion:The mechanism by which dexmedetomidine attenuates endotoxin-induced ALI may be related to inhibition of pyroptosis and reduction of inflammatory responses in rats.
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Objective:To evaluate the role of spinal peroxisome proliferation-activated receptor-γ (PPAR-γ) in protectin D1 (PD1)-induced reduction of neuropathic pain (NP) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (Sham group), NP group, NP plus PD1 group (NP+ PD group), and NP plus PD1 plus GW9662 group (NP+ PD+ GW group). Neuropathic pain was induced by spared nerve injury in anesthetized rats.In NP+ PD and NP+ PD+ GW groups, PD1 900 ng (diluted to 20 μl in dimethyl sulfoxide [DMSO]) was intrathecally injected once a day for 8 consecutive days starting from 30 min before establishing the model.In NP+ PD+ GW group, the PPAR-γ antagonist GW9662 200 ng (diluted to 20 μl in DMSO) was intrathecally injected once a day for 8 consecutive days starting from 45 min before establishing the model.The equal volume of DMSO was intrathecally injected in Sham group.The mechanical paw withdrawal threshold (PWT) was measured before establishing the model and at 1, 3, 5, 7, 10 and 14 days after establishing the model.Six rats in each group were sacrificed on day 14 after establishing the model, and their lumbar enlargements were removed for determination of the expression of PPAR-γ, TNF-α and IL-6 by Weston blot.Six rats in each group were sacrificed on day 14 after establishing the model, L 4, 5 segments of the spinal cord were removed, and the co-expression of PPAR-γ with neuron-specific nucleoprotein (NeuN), glial fibrillary acidic protein (GFAP) or serum calcium binding adapter molecule 1 (Iba-1) was determined by immunofluorescence staining. Results:Compared with group Sham, PWT was significantly decreased at each time point after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in the other three groups ( P<0.05). Compared with group NP, PWT was significantly increased at 7-14 days after establishing the model, the expression of PPAR-γ was up-regulated, and the expression of TNF-α and IL-6 was down-regulated in group NP+ PD, and no significant change was found in the parameters mentioned above in group NP+ PD+ GW ( P>0.05). Compared with group NP+ PD, PWT was significantly decreased at 7-14 days after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in group NP+ PD+ GW ( P<0.05). The results of immunofluorescence staining of the spinal cord showed that PPAR-γ was co-expressed with NeuN and GFAP. Conclusion:The mechanism by which PD1 mitigates NP is related to promoting the activation of PPAR-γ in spinal cord neurons and astrocytes and inhibiting inflammatory responses in rats.
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Objective To evaluate the effect of desflurane-remifentanil anesthesia on balance between cerebral oxygen supply and demand during cerebral revascularization in the patients with moyamoya disease.Methods Forty patients of both sexes with moyamoya disease,aged 18-64 yr,with body mass index of 18-25 kg/m2,undergoing superficial temporal artery-middle cerebral artery anastomosis,were allocated into 2 groups using a random number table method:desflurane-remifentanil group (D group) and propofol-remifentanil group (P group),with 20 cases in each group.Anesthesia was induced by intravenously injecting etomidate 0.3 mg/kg,sufentanil 0.4-0.5 μg/kg,and cis-atracurium 0.15-0.2 mg/kg.The patients were mechanically ventilated after tracheal intubation,and the end-tidal pressure of carbon dioxide was maintained at 35-45 mmHg.Anesthesia was maintained with propofol 4-6 mg · kg-1 · h-1 (group P),4％-6％ desflurane (group D),remifentanil 0.1-0.3 μg· kg-1 · min-1,remifentanil 0.1-0.3 μg · kg-1 · min-1 and intermittent intravenous boluses of cis-atracurium,and BIS value was maintained at 40-60.At 15 min after intubation (T1),30 min after skin incision (T2),immediately after opening the dura mater (T3),immediately after vascular bypass and patency (T4),and at the end of surgery (T5),blood samples were obtained from the radial artery and internal jugular bulb for blood gas analysis,jugular venous oxygen saturation (SjvO2) was recorded,and arteriovenous blood O2 content difference (Da-jvO2) and cerebral O2 extraction rate (CERO2) were calculated.Results Compared with group P,Da-jvO2 at T3-6 and CERO2 at T4-6 were significantly decreased,and SjvO2 was increased at T4-6 in group D (P＜0.05).Compared with the value at T1,Da-jvO2 was significantly decreased,and SjvO2 was increased at T5 in group D (P＜0.05).CERO2 was significantly lower,and SjvO2 was higher at T5 than at T3 in group P (P＜0.05).Compared with the values at T4,CERO2 was significantly decreased,and SjvO2 was increased at T5 in P and D groups (P＜ 0.05).Conclusion Compared with propofol-remifentanil anesthesia,desflurane-remifentanil anesthesia can maintain the balance between cerebral oxygen supply and demand better during cerebral revascularization in the patients with moyamoya disease.
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Objective To evaluate the effect of dexmedetomidine on the long-term sensorimotor gating system after sevoflurane anaesthesia in neonatal rats.Methods One hundred forty-four clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 4 groups (n =36 each) using a random number table method:control group (group C),sevofluraue group (group S),dexmedetomidine plus sevoflurane group (group D + S),and dexmedetomidine plus α2 receptor antagonist atipamezole plus sevoflurane group (group D+A+S).In group S,anesthesia was induced with 6％ sevofluraue for 3 min and maintained with 2.1％ sevoflurane,and the anesthesia time was 6 h in total.Dexmedetomidine 25 μg/kg was intraperitoneally injected in group D.In group D +A+ S,dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected,and the other treatments were similar to those previously described in group S.Twelve rats in each group were randomly selected after anesthesia and sacrificed,and blood samples were collected for determination of serum corticosterone concentrations by enzyme-linked immunosorbent assay.Twenty-four rats were randomly selected in each group,and prepulse inhibition (PPI) of startle test was performed at 70 days after birth.PPI rate (PP3％,PP6％,PP12％) was calculated.The serum corticosterone concentration was measured by restraint stress test on 80 days after birth.Results There was no significant difference in PP6％ or PP12％ among the four groups (P＞0.05).Compared with group C,PP3％ was significantly decreased,and the serum corticosterone concentration was increased after the end of anesthesia and during restraint stress test at 80 days after birth in S and D+A+ S groups (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group S,PP3％ was significantly increased,and the serum corticosterone concentration was decreased after the end of anesthesia and during restraint stress test at 80 days after birth in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group D+ A+S (P＞0.05).Compared with group D,PP3％ was significantly decreased,and the serum corticosterone concentration was increased after the end of anesthesia and during restraint stress test at 80 days after birth in group D+A+S (P＜0.05).Conclusion Dexmedetomidine can alleviate the damage to long-term sensorimotor gating system after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating central α2 receptors and improving hypothalamic-pituitary-adrenal axis hyperfunction.
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Objective To evaluate the role of Toll-like receptor 4 ( TLR4)/nuclear factor kappa B ( NF-κB) signaling pathway in the development of postoperative chronic pain and the relationship with ex-pression of voltage-gated sodium channel 1. 7 (Nav 1. 7) in the dorsal root ganglion (DRG) of rats. Meth-ods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: control group ( group C) , normal saline group ( group NS) and TLR4 antagonist LPS-RS group ( group R) . Postoperative chronic pain was produced by skin/muscle incision and retraction (SMIR). From 1 day before SMIR to 10 days after SMIR, NS group received continuous intrathecal injection of normal saline 10μl, while R group received continuous intrathecal injection of LPS-RS 20μg/10μl. Six rats were randomly selected in each group, and the mechanical pain threshold was measured at 1 day before SMIR and 1, 5, 10, 15 and 20 days after SMIR. The 6 rats left in each group were sacrificed at day 10 after SMIR, and the DRGs of the lumbar seg-ment (L4,5) were removed for determination of the expression of phosphorylated NF-κB (p-NF-κB) and Nav 1. 7. Results Compared with group C, the mechanical pain threshold was significantly decreased at 5-20 days after SMIR, and the expression of p-NF-κB and Nav1. 7 was up-regulated at 10 days after SMIR in group NS ( P＜0. 01) . Compared with group NA, the mechanical pain threshold was significantly increased at 5-20 days after SMIR, and the expression of p-NF-κB and Nav 1. 7 was down-regulated at 10 days after SMIR in group R (P＜0. 01). Conclusion Up-regulated expression of Nav1. 7 in DRGs after activating TLR4/NF-κB signaling pathway is involved in the development of postoperative chronic pain in rats.
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Objective To evaluate the effect of bilateral thoracic paravertebral block (TPVB) combined with general anesthesia on early recovery after Nuss procedure in patients with pectus excavatum.Methods Sixty patients of both sexes with pectus excavatum,aged 8-18 yr,with body mass index＜ 18.5-32.0 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective Nuss procedure,were divided into 2 groups by using a random number table method:general anesthesia group (group GA,n=30) and bilateral TPVB combined with general anesthesia group (group TPVB+ GA,n=30).Bilateral TPVB was performed at the level of T5 under ultrasound guidance at 30 min before operation in group TPVB+GA.Anesthesia was induced by intravenous injection of fentanyl,propofol and rocuronium and maintained by inhalation of sevoflurane,intravenous infusion of remifentanil 0.1-0.5 μg · kg-1 · min-1,and intermittent intravenous boluses of rocuronium.Patients received patient-controlled intravenous analgesia after operation.Tramadol 1-2 mg/kg or dizocin 0.1 mg/kg was intravenously injected as rescue analgesic,maintaining visual analogue scale score ≤ 3 within 2 days after operation.The intraoperative consumption of remifentanil,postoperative consumption of snfentanil,requirement for rescue analgesia and development of nausea and retching/vomiting were recorded.Quality of recovery was assessed using the Quality of Recovery-15 at 1 and 2 days after operation.Results Compared with group GA,the intraoperative consumption of remifentanil,postoperative consumption of sufentanil,rate of rescue analgesia and incidence of nausea and vomiting were significantly decreased,and Quality of Recovery-15 scores were increased at 1 and 2 days after operation in group TPVB +GA (P＜0.05).Conclusion Bilateral TPVB combined with general anesthesia can reduce the perioperative consumption of opioids and is beneficial for the early recovery after Nuss procedure in patients with pectus excavatum.
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Objective@#To evaluate the safety and efficiency of patient-controlled intravenous analgesia (PCIA) using hydromorphone supplement with dexmedetomidine on patients undergoing transcatheter arterial chemoembolization.@*Methods@#One hundred and eighty patients, age ranged from 40 to 65 years, body mass index from 18 to 25 kg/m2, ASA physical status Ⅱ-Ⅲ, who were scheduled for transcatheter arterial chemoembolization (TACE) under monitor anesthesia care (MAC) were randomly divided into 3 groups: hydromorphone group (H group), hydromorphone supplement with dexmedetomidine 1 μg/kg group (D1 group), hydromorphone supplement with dexmedetomidine 2 μg/kg group (D2 group), 60 patients in every group. All the groups of patients received PCIA pump, in the H group, the PCIA reagent was composed of 120 μg/kg hydromorphone and 5 mg tropisetron in 100 ml of normal saline. In comparison, PCIA regiment was composed of 120 μg/kg hydromorphone, 1 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D1 group, while 120 μg/kg hydromorphone, 2 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D2 group. The visual analogue scale (VAS) score, the observer′s assessment of alertness/sedation scale (OAA/S) score, patients′ satisfaction index, consumption of hydromorphone, the additional dose of morphine, the effective pressing times of PCIA and adverse reactions were recorded in detail at 0, 0.5, 1, 4, 12 and 24 hours after the patients underwent TACE.@*Results@#The total consumptions of hydromorphone were (4.3±0.1), (4.1±0.1), and (3.8±0.1) mg in group H, D1, and D2, respectively, and the effective pressing times were 13±3, 6±2 and 2±1, the additional doses of morphine were (30±5), (15±3), and (3±1) mg, and adverse reaction rates were 45.0%, 28.3%, and 10.0%, respectively. The manifestations mentioned above in D2 group were significantly lower than those in group H and group D1 (P<0.05). Immediately and 5 min after embolization, at the end of surgery and 0.5, 1, 4, 12 and 24 h after surgery, the VAS scores in the D2 group were 1.9±0.2, 2.1±0.3, 1.8±0.4, 1.8±0.3, 1.7±0.3, 1.6±0.3, 1.3±0.2, 1.3±0.3, respectively, lower than those in group H and group D1 (P<0.05); The satisfaction index in D2 group at these times were 8.7±1.1, 8.9±0.8, 9.2±0.9, 9.0±0.7, 9.1±0.8, 9.0±0.6, 9.1±0.7, 9.2±0.9, respectively, higher than those in group H and group D1 (P<0.05). No breath depression happened in these three groups.@*Conclusion@#The formula of hydromorphone combined with dexmedetomidine to patients undergoing TACE is greatly safe and efficient, with advantages in alleviating pain, reducing hydromorphone consumption and the incidence of adverse reaction of hydromorphone, and without breath depression.
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Objective To evaluate the role of C-X-C chemokine receptor type 4 ( CXCR4) in the dorsal root ganglia ( DRG) in incisional pain in rats. Methods Thirty-two male Sprague-Dawley rats, aged 7-10 weeks, weighing 250-300 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups (n＝8 each) using a random number table method: sham operation group (group S), CXCR4 antagonist AMD3100 plus sham operation group (group A+S), incisional pain group (group I) and CXCR4 antagonist AMD3100 plus incisional pain group (group A+I). Rats were anesthetized with sevoflu-rane. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and no incision was made 30 min later in group A+S. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the left hindpaw in group I. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and 30 min later the model of incisional pain was established in group A+I. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before surgery and 2, 4, 8, 16 and 24 h after surgery. The rats were sacrificed after the last measurement of pain threshold and the DRGs of the lumbar segment (L4-6) were removed for detecting the expression of CXCR4, phosphorylated extracellular regulated protein kinase ( p-ERK) and total ERK ( t-ERK) by Western blot. Results Compared with group S, MWT was significantly decreased and TWL was shortened at T1-5in group I and group A+I, and the expression of CXCR4 and p-ERK in DRGs was significantly up-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group I, no significant change was found in the expression of CXCR4, p-ERK and t-ERK in group A+I, and no significant change was found in the parameters mentioned above in group A+S (P＞0. 05). Compared with group I, MWT was significantly increased and TWL was prolonged at T1-5, the expression of CXCR4 and p-ERK in DRGs was down-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group A+I (P＞0. 05). Conclusion CXCR4 in DRGs is involved in incisional pain, and the mechanism may be re-lated to activating ERK1∕2 signaling pathway in rats.
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Objective To evaluate the effect of dexmedetomidine on sevoflurane anesthesia-in-duced cortical epileptiform electroencephalogram ( EEG) activity in the neonatal rats. Methods Forty clean-grade healthy Sprague-Dawley rats, aged 4-6 days, weighing 8-15 g, were divided into 5 groups (n＝8 each) using a random number table method: control group ( C group), sevoflurane group ( S group), dexmedetomidine plus sevoflurane group (D+S group), dexmedetomidine plus alpha 2-adrenocep-tor antagonist atipamezole plus sevoflurane group (D+A+S group), and atipamezole plus sevoflurane group (A+S group). After the electrode was correctly placed, the EEG was continuously monitored, and normal saline 5 μl∕g was intraperitoneally injected at 58 min of monitoring in group C, dexmedetomidine 25 μg∕kg was intraperitoneally injected in group D+S, dexmedetomidine 25 μg∕kg and atipamezole 250 μg∕kg were intraperitoneally injected in group D+A+S, and atipamezole 250 μg∕kg was intraperitoneally injected in group A+S. Anesthesia was induced by inhaling 6% sevoflurane for 3 min starting from 60 min of monitoring and then maintained by inhaling 2. 1% sevoflurane for 1 h. The total duration, the number and average du- ration of epileptic waves were recorded during anesthesia. Blood samples were obtained from the left ventri-cle after the end of anesthesia for blood gas analysis. Rats were then sacrificed and blood samples were col-lected for measurement of the serum corticosterone concentration. Results No epileptic wave was found in group C. The serum concentration of corticosterone was significantly higher in the other four groups than in group C ( P＜0. 05). Compared with group S, the total duration of epileptic wave was significantly short-ened, the number of epileptic wave was reduced, and the concentration of corticosterone was decreased in group D+S (P＜0. 05), and no significant change was found in the total duration, the number and average duration of epileptic waves or serum concentration of corticosterone in D+A+S and A+S groups (P＞0. 05). Compared with group D+S, the total duration of epileptic wave was significantly prolonged, the number of epileptic wave was increased, and the serum concentration of corticosterone was increased in D+A+S and A+S groups (P＜0. 05). Conclusion Dexmedetomidine can inhibit the occurrence of cortical epileptiform EEG activity induced by sevoflurane anesthesia in the newborn rats, and the mechanism may be related to improving the hypothalamus-pituitary-adrenocortical axis hyperfunction mainly through activating the central 2-adrenoceptor.
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Objective To evaluate the effect of dexmedetomidine on postoperative pain in rats with preoperative sleep deprivation. Methods Fifty healthy adult male Sprague-Dawley rats, aged 12 - 14 weeks, weighing 200-300 g, were divided into 5 groups ( n = 10 each) using a random number table:control group (group C), sleep deprivation group (group SD), incisional pain group (group IP), sleep deprivation plus incisional pain group ( group SD + IP) and sleep deprivation plus incisional pain plus dexmedetomidine group (group SD+IP+DEX). Sleep deprivation was induced by the flower pot technique, and then the incisional pain model was carried out on first day after completion of sleep deprivation. Dexme-detomidine 50 μg∕kg was intraperitoneally injected for 3 consecutive days before establishing the model of in-cisional pain in group SD+IP+DEX, and the equal volume of normal saline was given in the other groups. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal threshold ( TWT) were measured before operation or at 1 day before sleep deprivation and after operation or at 12, 24 and 72 h af-ter sleep deprivation. Blood samples were collected and spinal cord tissues were removed after the end of be-havior test for determination of serum corticosterone concentrations (by enzyme-linked immunosorbent assay and content of 5-hydroxytryptamine (5-HT) in spinal dorsal horns (by high-performance liquid chromatogra-phy). Results Compared with group C, the MWT and TWT were significantly decreased, and the serum corticosterone concentrations and content of 5-HT in spinal dorsal horns were increased in the other 4 groups(P<0. 05). Compared with group IP, the MWT and TWT were significantly decreased, and the serum cor-ticosterone concentrations and content of 5-HT in spinal dorsal horns were increased in group SD+IP, and the MWT and TWT were significantly increased (P<0. 05), and no significant change was found in the ser-um corticosterone concentrations or content of 5-HT in spinal dorsal horns in group SD + IP + DEX ( P >0. 05). Compared with group SD+IP, the MWT and TWT were significantly increased, and the serum cor-ticosterone concentrations and content of 5-HT in spinal dorsal horns were decreased in group SD+IP+DEX (P<0. 05). Conclusion Dexmedetomidine can reduce postoperative pain in rats with preoperative sleep deprivation, and the mechanism may be related to inhibiting stress responses and levels of 5-HT in spinal dorsal horns.
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Objective To evaluate the effect of dexmedetomidine on the long-term anxiety state after sevoflurane anesthesia in neonatal rats and the role of different central subtypes of α2 receptors.Methods A total of 216 clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 6 groups (n =36 each) using a random number table method:control group (group C),sevoflurane group (group S),dexmedetomidine + sevoflurane group (group D+S),dexmedetomidine + α2 receptor antagonist atipamezole + sevoflurane group (group D+A+S),dexmedetomidine + α2A receptor antagonist BRL44408 + sevoflurane group (group D+B+S),and dexmedetomidine + α2C receptor antagonist JP1302 + sevoflurane group (group D+J+S).Anesthesia was induced by inhaling 6％ sevoflurane for 3 min and maintained by inhaling 2.1％ sevoflurane for 6 h.At 30 min before anesthesia induction,dexmedetomidine 25 μg/kg was intraperitoneally injected in group D+S,dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected in group D + A + S,dexmedetomidine and α2A receptor antagonist BRL44408 1.5 mg/kg were intraperitoneally injected in group D+B+S,and dexmedetomidine 25 μg/kg and α2C receptor antagonist JP1302 3 mg/kgwere intraperitoneally injected in group D+J+S.Twelve rats in each group were randomly selected and sacrificed after the end of anesthesia,blood samples were collected for blood gas analysis,and the serum corticosterone concentration was measured by enzyme-linked immunosorbent assay.The elevated plus maze was performed when the left rats in each group were 60 days old,and 12 rats were selected when the they were 80 days old to perform the restraint stress test.Results Compared with group C,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in S,D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in D+S and D+J+S groups (P＞0.05).Compared with group S,the percentage of time of staying at the open arm was significantly increased,the total motion distance was prolonged,and the serum corticosterone concentration was decreased after the end of anesthesia and during the restraint stress test in group D+S and group D+J+S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+A+S and group D+B+S (P ＞0.05).Compared with group D+S,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in group D+J +S (P＞ 0.05).Conclusion Dexmedetomidine can reduce the long-term anxiety state after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating central α2A receptors and improving hypothalamic-pituitary-adrenocortical axis hyperfunction.
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Objective To evaluate the efficacy of dexmedetomidine mixed with sufentanil for patient-controlled intravenous analgesia (PCIA) in the patients undergoing transcatheter hepatic arterial chemoembolization (TACE).Methods One hundred and twenty patients of both sexes,aged 40-65 yr,weighing 45-80 kg,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective TACE under monitored anesthesia care,were divided into 2 groups (n =60 each) using a random number table:sufentanil group (S group) and dexmedetomidine mixed with sufentanil group (DS group).At 15 min prior to surgery,0.1 μg/kg sufentanil and 5 mg tropisetron were intravenously injected in both groups.In addition,dexmedetomidine 0.6 μg/kg was intravenously infused for 15 min in DS group,while the equal volume of normal saline was given instead in S group.PCIA solution contained sufentanil 2 μg/kg and tropisetron 5 mg in 100 ml of normal saline in S group.PCIA solution contained sufentanil 2 μg/kg,dexmedetomidine 2.μg/kg and tropisetron 5 ng in 100 ml of normal saline in DS group.The PCIA pump was programmed to deliver a 0.5 ml bolus dose with a lockout interval of 15 min and background infusion of 2 ml/h.Observer's Assessment of Alertness/Sedation Scale scores and scores for patient's satisfaction with analgesia were recorded at 30 min and 2,6,12,24 and 48 h after surgery.The pressing times of PCIA,total consumption of sufentanil and requirenent for morphine as rescue analgesics were recorded.The development of requirement for antiemetics,nausea and vomiting,bradycardia,respiratory depression and agitation was also recorded during analgesia.Results Compared with S group,the pressing times of PCIA,total consumption of sufentanil and requirement for morphine were significantly reduced,scores for satisfaction with analgesia were increased,and Observer's Assessment of Alertness/Sedation Scale scores were decreased (P＜0.05),and no significant change was found in the incidence of nausea and vomiting,additional requirement for antiemetics,bradycardia,respiratory depression or agitation in DS group (P＞0.05).Conclusion Dexmedetomidine mixed with sufentanil produces better efficacy than sufentanil alone when used for PCIA in the patients undergoing TACE.
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Objective To investigate the effect of PXR* 1B polymorphism on postoperative analgesia with fentanyl in the patients undergoing gynecological operation.Methods A total of 102 female patients from Henan province, of Han nationality, aged 20-50 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , with body mass index of 14.8-30.0 kg/m2, scheduled for elective abdominal total hysterectomy or myomectomy under general anesthesia, were enrolled in this study.PXR genetic polymorphic sites were analyzed by polymerase chain reaction (PCR)-direct DNA sequencing.PXR* 1B haplotype was analyzed by the PHASE V.2.1 software.The patients were assigned into 3 groups according to their genotypes: PXR* 1B haplotype group (group PXR* 1B), non-PXR* 1B haplotype group (group n-PXR* 1B) and PXR* 1B/PXR * 1B group (group PXR* 1B/PXR* 1B).Postoperative pain was assessed with visual analogue scale (VAS) score.When VAS ＞ 3, fentanyl 20 μg was injected intermittently until VAS ≤ 3, and then a pump was connected to perform patient-controlled intravenous analgesia (PCIA) with fentanyl.PCIA solution contained fentanyl 1.0 mg and droperidol 5 mg in 100 ml of normal saline.The PCA pump was set up with a 2 ml bolus dose, a 5 min lockout interval and background infusion at a rate of 0.5 ml/h.The number of successfully delivered doses was set at 7 times, and the maximal amount of fentanyl was 145 μg.If exceeding the maximal dose, the VAS score was still more than 3, nonsteroidal anti-inflammatory drugs were given as rescue medication.VAS score immediately after the end of operation, and the consumption of fentanyl within 24 h after operation were recorded.Midazolam 0.1 mg/kg was injected intravenously during induction of general anesthesia, and 1 h later venous blood samples were collected for determination of plasma 1'-hydroxymidazolam and midazolam concentrations.The ratio of 1'-hydroxymidazolam concentration to midazolam concentration was calculated to reflect the activity of CYP3A4.Results No patients required rescue anesthetics in the three groups.There were 27 cases in group PXR * 1B, 53 cases in group n-PXR* 1B, and 22 cases in group PXR* 1B/PXR* 1B.PXR* 1B allele frequency was 37.2％.There was no significant difference in VAS score immediately after the end of operation, consumption of fentanyl within 24 h after operation, and activity of CYP3A4 between the three groups (P＞0.05).Conclusion PXR* 1B polymorphism has no effect on postoperative analgesia with fentanyl in the patients undergoing gynecological operation, and is not one of the genetic factors producing individual variation in postoperative analgesia.
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Objective To evaluate the effect of dexmedetomidine on cognitive dysfunction after thoracic surgery in patients undergoing one-lung ventilation.Methods Sixty-two patients,aged 45-64 yr,of ASA physical status Ⅰ or Ⅱ,with body mass index ranged from 17.5 to 25.5 kg/m2,scheduled for elective thoracic surgery,were randomly allocated into 2 groups (n =31 each) using a random number table:dexmedetomidine group (Dex group) and control group (C group).Dexmedetomidine 0.5 μg/kg was infused for 10 min starting from the time point before induction of anesthesia,followed by continuous infusion at a rate of 0.5 μg · kg-1 · h-1 until 30 min before the end of surgery in Dex group.The equal volume of normal saline was administered instead in group C.Before induction and at 24,48 and 72 h after surgery,venous blood samples were collected for determination of levels of S-100 beta protein and neuronspecific enolase in serum by ELISA.Cognitive function was assessed by Mini-Mental State Examination at 72 h after surgery.Results The levels of S-100 beta protein and neuron-specific enolase in serum were significantly increased after surgery than before induction in the two groups.Compared to C group,the levels of S-100 beta protein and neuron-specific enolase in serum were significantly decreased after surgery,and the incidence of postoperative cognitive dysfunction was decreased in Dex group (26％ vs 6％).Conclusion Dexmedetomidine can effectively reduce the nerve damage during one-lung ventilation and significantly inhibit the development of postoperative cognitive dysfunction in patients undergoing thoracic surgery,indicating that dexmedetomidine is suitable for thoracic surgery.
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Objective To evaluate the reliability of autologous blood withdrawal during cesarean section. Methods Fifteen patients preoperatively diagnosed with pernicious placenta previa and∕or accrete by using ultrasound and magnetic resonance imaging, aged 20-35 yr, weighing 55-75 kg, at≥36 weeks of gestation, were enrolled in the study. Blood containing amniotic fluid from the surgical field was collected, and the washed blood was processed using cell?salvage machine and then filtered using a leukocyte depletion filter during cesarean section. The 20 ml blood samples collected included maternal central venous blood after delivery of fetus, unwashed blood, washed blood and filtered blood. The fetal squamous cells were counted using papanicolaou staining. The concentrations of a?fetoprotein, tissue factor, endothelin?1 and histamine were measured by enzyme linked immunosorbent assay. The fetal red blood cells were counted using the acid elution method and HE staining. Results Compared with unwashed samples, the tissue factor concentrations were significantly increased, and the fetal squamous cell count, concentrations of a?fetoprotein and endothelial?1, and fetal red blood cells were decreased in the washed samples. Compared with washed samples, the fetal squamous cell count, concentrations of a?fetoprotein and fetal red blood cells were significantly decreased in filtered samples. Compared with maternal venous blood samples, the tissue factor concentrations were significantly increased, and the fetal squamous cell count and concentrations of a?fetoprotein and endothelial?1 were decreased in filtered samples. Conclusion Autologous blood withdrawn during cesarean section can be used for reinfusion in cesarean section.
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Objective To establish in vitro metabolism of fentanyl by human liver microsomes in Chinese population.Methods Thirty patients undergoing elective operation on liver were enrolled in the study.Normal liver specimens were obtained during removal of liver and gall for preparation of liver microsomes (by calcium precipitation) which were used for establishment of the liver microsomal incubation system for fentanyl.Fentanyl served as the metabolic substrate in the incubation reaction.The concentration of fentanyl in the incubation medium was detected at 0,5,10,15,20 and 30 min of incubation using HPLC-UV.Sufentanil served as the interior label element.The n-hexane-ethanol absolute was used to extract the sample.The chromatographic column used in this method was Grace C18 (4.6 mm × 250.0 mm,5 μm).The mobile phase was methyl cyanide-KH2PO4 buffer solution with the flow rate of 1.0 ml/min,detection wavelength of 205 nm and sample size of 20 μl.Linear regression analysis was performed by using the least-squares method.The specimens of the blank incubation system with the final concentration of fentanyl 0.6,2.4 and 10.0 μg/ml were obtained to determine the recovery,precision and stability.The metabolic rate of fentanyl in human hepatic microsomes was calculated.Results Fentanyl and the interior label element sufentanil were separated completely,and the retention time were 5.730 and 9.336 min,respectively.Endogenous matrix of microsomes did not interfere with the analysis.Regression equation was C =0.945 8A-0.140 4,R2 =0.999 2.C was the concentration of fentanyl,and A was the peak area ratio of fentanyl versus sufentanil.The recovery of incubation system with low,medium and high concentrations of fentanyl was 85％-115％,and relative standard deviation (RSD) was less than 10％.The RSD of intra-and inter-day precision and stability was less than 10％.The method was proved to meet the requirements of biological sample analysis.The metabolic rate of fentanyl was (1.6 + 0.8) nmol/min per milligram protein in human hepatic microsomes of 30 cases.Conclusion The in vitro metabolism of fentanyl by human liver microsomes is convenient,and the detectability is high,so it can be used for the research on the in vitro metabolism of fentanyl in Chinese population.
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Objective To investigate the optimum concentration and dose of ropivacaine for caudal block in the neonates undergoing laparotomy under general anesthesia.Methods One hundred pediatric patients of both sexes,aged 9-30 days,weighing 2.5-4.5 kg,scheduled for elective pyloromyotomy,were randomly divided into 5 groups (n =20 each) using a random number table:control group (group C),0.10％ ropivacaine 1.0 ml/kg group (group 0.1％ L1),0.15 ％ ropivacaine 1.0 ml/kg group (group 0.15 ％ L1),0.10 ％ ropivacaine 1.2 ml/kg group (group 0.10 ％ L2),and 0.15 ％ ropivacaine 1.2 ml/kg group (group 0.15 ％ L2).Anesthesia was induced with sevoflurane and cisatracurium.The pediatric patients were tracheally intubated and mechanically ventilated.Remifentanil was infused intravenously at 0.2-0.3 μg· kg-1 · min-1 in group C.In 0.10 ％ L1,0.15 ％ L1,0.10 ％ L2 and 0.15％L2 groups,the corresponding concentrations and doses of ropivacaine were injected into the sacral canal under the guidance of ultrasound.The operation was started at 15 min after administration and sevoflurane was inhaled and the end-tidal concentration of sevoflurane was maintained at 0.8-1.0 MAC.Before induction (T1),at pyloric muscle retraction (T2),and at 4,8,12 and 24 h after operation (T3-6),blood samples were collected from the central vein for determination of plasma concentrations of cortisol and interleukin-6 (IL-6).Pain was assessed using CRIES score at T3-6.When CRIES scores ＞ 3,10％ chloral hydrate 0.5 ml/kg was given by retention enema for analgesia,and the requirement for chloral hydrate was recorded.The emergence time,extubation time,duration of stay in post-anesthesia care unit (PACU) and hospital discharge time were recorded.Bradycardia and hypotension during operation,and development of motor block of lower extremities,infection and dehiscence of incision,vomiting,and urinary retention after operation were also recorded.Results Compared with group C,no significant changes were found in the emergence time,extubation time,duration of stay in PACU,hospital discharge time,plasma concentrations of cortisol and IL-6,the requirement for chloral hydrate,and the incidence of bradycardia,hypotension,motor block of lower extremities,and infection and dehiscence of incision in 0.10％ L1 and 0.15 ％ L1 groups,the emergence time,extubation time,duration of stay in PACU,hospital discharge time were significantly shortened,and the plasma concentrations of cortisol and IL-6,requirement for chloral hydrate,and the incidence of hypotension and infection of incision were decreased in 0.10％ L2 and 0.15％ L2 groups,and the incidence of vomiting and urinary retention was increased in 0.15％ L1 and 0.15％ L2 groups.Compared with group 0.10％ L2,the incidence of vomiting and urinary retention was significantly decreased,and no significant changes were found in the other parameters mentioned above in 0.15％ L2 group.Conclusion The optimum concentration and dose of ropivacaine are 0.10％ and 1.2 ml/kg,respectively,for caudal block in the neonates undergoing laparotomy under general anesthesia.
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Objective To evaluate the effects of inhalation anesthesia with low-flow sevoflurane on the renal function of neonates.Methods Forty ASA physical status Ⅰ or Ⅱ neonates undergoing abdominal surgery under general anesthesia,aged 6-28 days,weighing 1730-2928 g,were included in the study.After induction of anesthesia,anesthesia was maintained with sevoflurane inhalation using a semi-closed circuit system (FGF 1 L/min).The end-tidal concentration of sevoflurane was maintained at 2.5％-4.0％ according to the vital signs.Before induction of anesthesia,immediately after operation,and at 24,48 and 72 h after operation,blood samples from the peripheral vein and urine specimens were taken for determination of serum concentrations of creatinine (Cr),blood urea nitrogen (BUN),urinary retinol binding protein (RBP) and β-N-acetyl-glucosaminidase (NAG).A temperature probe was inserted to the center of soda lime canister.Results Compared with the baseline value at T0,no significant changes were found in the serum Cr and BUN concentrations at T1-4,urinary RBP concentrations were increased at T1,no significant changes were found in urinary RBP concentrations at T2-4,NAG concentrations were significantly increased at T2 and no significant changes were found in NAG concentrations at T1,3,4.The temperature of soda lime was (37 ± 3) ℃ at the end of operation.Conclusion Inhalation anesthesia with low-flow sevoflurane (FGF 1 L/min) produces no significant effect on the renal function of neonates.