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Neurosteroids are synthesized from cholesterol within the microglia of the central nervous system. They are classi?fied as dehydroepiandrosterone,progesterone,pregnenolone,allopregnanolone and other peripheral steroids. Neurosteroids such as al?lopregnanolone are positive allosteric modulators of GABAA receptors and exert anxiolytic and antidepressant-like behavior. Neuroac?tive steroids play a significant role in neurodevelopment in terms of internal environment homeostasis. This paper reviews the biosynthe?sis,metabolism regulatory effect on the response to stress and therapeutic potentials of neurosteroids.
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OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.
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OBJECTIVE To investigate the effect of overexpession of 18 ku translocator protein (TSPO) on the hippocampal dentate gyrus. METHODS Lentiviral (LV) vectors containing TSPO or the lentiviral sequence were infused into the hippocampus bilateral dentate gyri (2 × 108 TU · mL-1,1 μL per side)of mice. Behavioral tests were carried out. The anxiolytic-like behavior of mice was examined by such means as the elevated plus maze test , the staircase test , light dark box test for 12, 14 and 16 d, two behavioral despair models, tail suspension test and the forced swimming test for 16 and 18 d,respec?tively. Western blotting and ELISA were used to evaluate the TSPO expression and the concentration of allopregnanolone in hippocampal tissue (3 mm in diameter around the injection site on both sides) at the end of tests. RESULTS The results of behavioral experiments showed that TSPO overexpression group deneloped anxiolytic and antidepression-like behavior. LV-TSPO significantly increased the retention time in the central area〔14 ± 4 vs (25 ± 12)s,P<0.05〕. LV-TSPO significantly increased the percentage of entry into open arms entries percentage and the percentage of time spent in open arms time without changing total entries and total time in the elevated plus-maze test〔(13±8)%vs (26±18)%, P<0.05;(6 ± 6)%vs (27 ± 6)%, P<0.05)〕. LV-TSPO significantly decreased the number of rearings without changing the number of steps in staircase test (21±7 vs 12±5,P<0.05). LV-TSPO increased entries into the light area and retention time in light-dark transition test〔(18 ± 8)% vs (26 ± 7)%, P<0.05;72 ± 36 vs (191 ± 90)s, P<0.05)〕but significantly decreased immobility time in the tail suspension test and forced swimming test〔94±33 vs (36±20)s, P<0.01;137±36 vs (90±37)s, P<0.05)〕, without excitatory or inhibitory actions on the central nervous system. At the same time, the level of TSPO expression in hippocampal tissues (3 mm in diameter around the injection site on both sides) was significantly increased, so did the concentration of allopregnanolone (P<0.05). CONCLUSION Overexpression of TSPO in the hippocamus dentate gyrus of mice can induce anxiolytic and antidepressant-like behavior, and the downstream allo?pregnanolone biosynthesis at least partially mediates the behavioral effects.
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OBJECTIVE To investigate the relationship between the anti-post-traumatic stress disorder(PTSD)effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline(15 mg · kg-1) intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and 7th day after the extinction training in rats. The NO contents were detected by Griess method and the nNOS and iNOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group ,the freezing time was significantly increased in extinction control group and extinction training group(P<0.01),indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline(15 mg·kg-1)group was decreased compared with extinction training group (P<0.05). At the 7th day,the freezing time was significantly decreased(P<0.01),indicating that ser?traline reversed the fear response. At the same time,the contents of NO,nNOS and iNOS on amygdala of rats in sertraline group were lower than that in extinction training group(P<0.01). CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has anti-PTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.
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γ-aminobutyric acid A(GABAA)receptor is one of the ligand-gated ion channel receptors expressing widely in the brain. As the major inhibitory neurotransmitter receptor, GABAA receptor is involved in the regulation of many physiological mechanisms. Imbalance expression of the receptor may lead to neuropsychiatric disorders such as schizophrenia,depression, epilepsy,post-traumatic stress disorder (PTSD) syndrome,neurofibromatosis type 1 and fragile X syndrome. Clinically classic benzodiazepines acting on GABAA receptor can be used for the auxiliary treatment of various neuropsychiatric disorders,which supports the potential therapeutic value of GABAA receptor for these diseases. The paper describes the molecular structure and subtypes of GABAA receptor and further reviews the progress in the link between GABAA receptor and neuropsychiatric disorders in order to provide a new target for the drug therapy development of neuropsychiatric disorders.
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Objective To investigate the effect of dezocine combined with fentanyl in patients undergoing kidney transplantation on the quality of anesthesia and recover consciousness,as well as explore the preemptive analgesia effect of dezocine in renal transplantation.Methods Eighty patients undergoing allogeneic renal transplantation were randomly divided into control group (Ⅰ) and dezocine group (Ⅱ) (40 cases for each group).Patients in two groups were induced with midazolam 0.05 mg/kg,propofol 1-2 mg/kg,fentanyl 3 μg/kg,and cis-atracurium 2.5 mg/kg intravenously,and then they were incubated and given mechanical ventilation.Anesthesia was maintained with intravenous and inhalational anesthesia.1％-2％ sevoflurane had been inhaled until half an hour before the end of the surgery,while 1％ propofol 3-5 mg/kg/h and remifentanil 0.1-0.2 μg/kg/min had been pumped intravenously till the end of the surgery.2μg/kg fentanyl was infused in control group,while in dezocine group 0.1 mg/kg dezocine was intravenously infused before skin incision.The concentration of sevoflurane and the pump speed ofremifentanil were adjusted according to the depth of anesthesia.Changes of mean arterial pressure (MAP),heart rate (HR) and the pulse oximetry (SPO2) before anesthesia (T0),before skin incision (T1),5 minutes after incision (T2),5 minutes before extubation (T3) and 10 minutes after extubation(T4) were recorded.Extubation time,nausea,vomiting and the incidence of adverse reactions during recovery period were also recorded.Before leaving the operating room,VAS scale was used to assess the pain situation of patients.Results There were no significant differences in terms of MAP,HR and SPO2 at each time point between two groups (P ＞ 0.05).The VAS scores in fentanyl group was 1.76 ± 0.43,as same as that in dezocine group (1.84 ± 0.57,P =0.480 7).The incidence of adverse reactions including nausea,vomiting in fentanyl group and dezocine group were 22.5％ and 2.5％,and the difference was significant (x2 =7.314 3,P =0.007).The extubationtime after surgery in diesoline group [(12.21 ± 2.16) min] was significantly shortened than that in fentanyl group [(15.15 ± 2.25) min],P =0.000).Conclusion Dezocine preemptive analgesia is used in renal transplant patients in advance,and it can partly replace the same effect of fentanyl analgesia intensity,significantly shorten the extubation time,reduce the occurrence of awakening period adverse events such as of nausea,vomiting and restlessness.It is safe for renal transplant patients.
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Objective To investigate the effects of controlled low central venous pressure (CLCVP) on cerebral oxygen metabolism during orthotopic liver transplantation (OLT),and study the safety of CLCVP in OLT.Method Forty-six patients subject to OLT were randomly divided into CLCVP group (CL group) and CVP group (C group).Blood samples were taken from radial artery and jugular simultaneously for blood gas analysis before operation (T1,baseline),immediately blocking inferior vena and portal vein (T2),30 min after anhepatic phase (T3),30 min after graft reperfusion (T4),2 h after graft reperfusion (T5),and 24 h after graft reperfusion (T6).Cerebral arterial oxygen content (CaO2),jugular oxygen content (CjvO2),cerebral arterial-venous oxygen content difference (Ca-jvO2),cerebral oxygen extraction rate (CERO2),and cerebral blood flow/ cerebral metabolic rate of oxygen (CBF/CMRO2) were calculated by the Fick formulae.Meanwhile,blood samples were taken from jugular simultaneously for serum creatinine (Cr) and urea nitrogen (BUN) a different time points.We also recorded the whole operation time,anhepatic phase time,volume of blood loss and transfusion,and urine volume.Results As compared with C group,CaO2,CjvO2,Ca-jvO2,SjvO2,CERO2 and CBF/CMRO2 in CL group were nearly not changed at different time pioints (P＞0.05),but in the same group,as compared with T1 and T2,the CaO2,CjvO2,Ca-jvO2 and CERO2 in T3,T4 and T5 were decreased significantly (P＜0.05),and the SjvO2 in T3,T4 and T5 was increased remarkably.The operation time and anhepatic phase time had no significant difference in both groups.As compared with C group,the volume of blood loss and transfusion in CL group were decreased (P＜0.05),and the urine volume in CL group CL was increased significantly (P＜0.05).Cr and BUN showed no significant difference in both groups and at the same time points of C group and CL group.Conclusion CLCVP can decrease volume of blood loss and transfusion,increase urine volume during OLT,and it does not change the cerebral oxygen metabolism during OLT.
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ObjectiveTo explore two different anesthesia methods on hemodynamics and the quality of palinesthesia in elderly patients during peroperative period.Methods Sixty elderly patients with Hip Replacement( ASA,Ⅰ,Ⅱ ) were randomly divided into general anesthesia group ( group A,n =30 ) and combined general and epidural anesthesia group( group B,n =30).The changes of mean arterial pressure(MAP)and heart rate( HR ) were monitored before induction of anesthesia( T1 ),at intubation( T2 ),during skin incision (T3) and at the time of extubation ( T4 ),at 30 min after extubation ( T5 ) and at the same time,the dosage of general anesthetics and each index's time after operation to awake were recorded of the patients in both groups.ResultsThe MAP and HR of patients in two groups at T2,T3,T4,T5 were all increased when compared with T1.And the increasing degree of MAP and HR in group A were higher than that in group B ( MAP:within group F =17.352,interaction F =4.326,between groups F =8.652; HR:within group F =11.561,interaction F =5.241 between groups F =7.248; P ＜ 0.05 ).The dosage of general anesthetics was significantly different between two groups[ sevoflurane:(1.40 ± 0.30)MAC vs (1.00 ± 0.12 )MAC,t =0.37,P＜0.05 ; fentanyl:(0.34 ±0.08)mg vs(0.18 ±0.03) mg,t =0.21,P ＜0.05 ; vecuronium:(6.20 ±0.32) mg vs(4.10 ±0.31 ) mg,t =1.24,P ＜0.05 ; propofol:(448 ±24) mg vs(393 ±26) mg,t =3.46,P ＜0.05].There was significant difference on gag reflex time [ ( 18.00 ± 1.27 ) min vs ( 12.31 ± 2.54 ) min,t =2.74,P ＜ 0.05 ],time to extubation [ ( 24.03 ± 2.42 ) min vs ( 16.05 ± 1.20 ) min,t =3.68,P ＜ 0.05 ],fully awake time [(29.54±5.24)min vs(19.25±2.64)min,t=1.35,P＜0.05] between these two groups.ConclusionThe two different anesthesia methods can ensure haemodynamic stability of elderly patients undergoing hip replacement during peroperative period.But compared with general anesthesia group,combined general and epidural anesthesia group can reduce the dosage of general anesthetics and shorten the time of extubation significantly,it is a viable and an ideal method.
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0.05),while in 75U/ml,100U/ml and 200U/ml groups,PF decreased significantly(P
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Objective To investigate the change in coagulation function in relation to different amounts of blood loss in selective non-cardiovascular surgery patients.Methods Twenty American Anesthesia Association (ASA) class I or Ⅱ patients,aged 23-57 yr,undergoing non-cardiovascular surgery with normal preoperative coagulation were chosen randomly.After general anesthesia,on the basis of adequate sedation and analgesia,patients were given Ringer's solution and Voluven (pre-warmed to 37℃,volume ratio of crystalloid/colloid was 1:2) to maintain the stability of heart rate,blood pressure and central venous pressure.Temperature and blood gas analysis were monitored to prevent potential interference induced by hypothermia and acidosis.When the ratio of blood loss/blood volume reached 10%,15%,20% and 25%,all the routine blood components analysis and coagubility parameters,and Sonoclot coagulation and platelet function parameters were observed.Results Preoperative average value of Hct was 38.1%,and when ratio of blood loss/blood volume were 10%,15%,20 % and 25%,Hct was decreased to 33.4%,31.5%,30.1% and 27.9% respectively.When the ratio reached 15% or larger,platelet count decreased significantly compared with preoperative value (P
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Objective To evaluate the protective effect of midazolam (MID) on PC 12 cells against injury induced by N-methyl-D-aspartate (NMDA) -Methods The differentiated PC12 cell strain was isolated and cultured in DMEM full nutrient liquid medium and incubated in CO2 incubator at 37℃ and 5 % CO2 for 3-4 days. The experiment consisted of 3 groups : (1) control group; (2) NMDA group and (3) MID treatment group. In NMDA group NMDA 300 ?mol?L-1 was added to DMEM liquid medium. MID group was further divided into five subgroups according to different concentrations of midazolam (MID) added to DMEM liquid medium in addition to NMDA 300 ?mol?L-1 :MID Ⅰ -Ⅴ subgroups (midazolam 0.33, 1, 3, 10, 30?mol?L-1 ). The PC 12 cells were then cultured for another few hours. Cellular viability was assessed by lactic dehydrogenase (LDH) assay and MTT assay. Meanwhile the [Ca2+ ] was measured by Fura-2/AM fluorescence and nitric oxide synthase (NOS) activity was measured with ultraviolet spectrophotometer. Results Exposure to NMDA 300 ?mol?L-1 for 4 h resulted in increase in release of LDH from PC 12 cells and decrease in optical density (OD570nm) absorbed by living cells, indicating that NMDA induced injury to PC12 cells. The presence of midazolam 0.33, 1, 3, 10 ?mol?L-1 ( MID subgroup I -IV ) decreased LDH release and increased OD570nm value. Exposure to NMDA 300 ?mol?L-1 for 4h also resulted in increase in intracellular Ca2+ concentration ([Ca2+ ];) and NOS activity in PC 12 cells. Midazolam 3 and 30?mol?L-1 significantly decreased [Ca2+ ]; and NOS activity as compared with NMDA group.Conclusion Midazolam can attenuate the NMDA-induced injury to PC12 cells, decrease the Ca2+ overloading and NOS activity in PC 12 cells. The inhibitory effects of midazolam on [Ca2+ ]; overloading and NOS activity may be involved in the mechanism of its protective action.
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Objective To observe the effect of midazolam (MID) on amino acid levels in cultured PC12 cells challenged by N-methyl-D-aspartate (NMDA), and to explore the possible protective action of midazolam which is an anesthetic. Methods Cultured PC12 cells were divided into control group, NMDA group, and MID group. In NMDA group, PC12 cells were challenged by 300?mol/L NMDA in vitro. In MID group, 3?mol/L or 30?mol/L of MID was added to the challenged PC12 cell culture, thus forming two subgroups. After being treated with NMDA 300?mol/L for 4 hours, the PC12 cells were collected, rinsed, levigated and centrifuged (12 000r/min for 20min, at 4℃), then the supernatant liquid was collected. The levels of amino acids were determined with high performance liquid chromatograpy (HPLC). Results After exposing to NMDA 300?mol/L for 4 hours, the level of glutamate released from PC12 cells rose significantly, whereas the level of glutamine, aparatate and glycine remained unchanged. In the presence of MID 3?mol/L and 30?mol/L for 4 hours, the level of glutamate was lowered significantly (P
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Objective To observe the influence of propofol on amino acid levels in cultured PC12 cells impaired by N-methyl-D-aspartate, and explore the possible protective action mechanism of anesthetic propofol. Methods The levels of amino acid were measured by high performance liquid chromatography (HPLC). Results After exposing to NMDA 300?mol/L for 4h, the release of glutamate levels from PC12 cells was increased significantly, whereas the release of glutamine, aspartate, and glysine levels remained unchanged. In the presence of propofol 12.5, 125?mol/L for 4h, the levels of glutamate decreased significantly (P
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Objective To determine the effect of ulinastatin on improving gastric mucosal perfusion during orthotopic liver transplantation. Methods Thirty patients undergoing orthotopic liver transplantation were randomly divided into control group (group C,n=15) and ulinastatin group (group U,n=15). In ulinastatin group,patients were intravenously administrated 4000U/kg ulinastatin immediately after entering the operating room and then the administration was continued with an injection pump with a dose of ulinastatin of 2000U/(kg?h) till the end of operation. Normal saline in the same volume and infusion rate was given to patients in control group. Blood pressure (BP),heart rate (HR),cardiac output (CO) and introgastric pH value (i-pH) plus Pg-aCO2 were measured before the operation (T0),20min of preanhepatic phase (T1),5 min of anhepatic phase (T2),30min of anhepatic phase (T3),5min of new hepatic phase (T4),30min of new hepatic phase (T5) and the end of operation (T6),respectively. Results Compared with the measurement at the time point of T0,mean artery pressure (MAP),central venous pressure (CVP) and CO were significantly decreased and complicated with a marked increase of HR at the time point of T2 in all patients of two groups (P