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Objective To evaluate the role of α2A adrenergic receptor (α2AAR) in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation (H/R)caused injury to alveolar type Ⅱ epithelial cells.Methods Type Ⅱ] alveolar epithelial cells of rats RLE6TN cells cultured in vitro were divided into 4 groups (n =6 each) using a random number table method:control group (group C),H/R injury group (group H/R),dexmedetomidine group (group D) and α2A AR small interfering RNA (siRNA) plus dexmedetomidine group (group α2AAR-siRNA+D).H/R was produced by exposing cells to 1％ O2-5％ CO2-94％ N2 for 24 h followed by 4-h reoxygenation.Cells were incubated for 1 h with dexmedetomidine at the final concentration of 1 nmol/L,and then H/R model was established in group D.In group α2AAR-siRNA+D,cells were transfected with 50 nmol/L α2AAR-siRNA,48 h later dexmedetomidine at the final concentration of 1 nmol/L was added,cells were incubated for 1 h,and then H/R model was established.The cell viability was measured using CCK-8 method,cell apoptosis rate was determined by flow cytometry,and the expression of TLR4 and NF-κB was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group H/R (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group H/R,the cell viability was significantly increased,the apoptosis rate was decreased,and the expression of TLR4 and NF-κB was down-regulated in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group α2AAR-siRNA+D (P＞0.05).Compared with group D,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group α2AAR-siRNA+D (P＜0.05).Conclusion The mechanism by which dexmedetomidine inhibits TLR4/NF-κB signaling pathway activation may be related to activating α2AAR during H/R-caused injury to alveolar type Ⅱ epithelial cells.
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AIM: To investigate the effect of rosiglitazone , a peroxisome proliferators-activated receptor γ(PPARγ) agonist, on the expression of PPARγ, the activation of NF-κB and intestine injury in the rats undergoing ortho-topic autologous liver transplantation ( OALT ) .METHODS: Sprague-Dawley male rats were randomly divided into 4 groups:control group, sham group, OALT group and rosiglitazone (0.3 mg/kg, iv) pretreatment (ROS+OALT) group. The OALT model was established , and the intestinal tissues were collected 8 h after the liver reperfusion .The intestinal tis-sue sections were stained to visualize the damage .The expression of PPARγand NF-κB in the tissues, the concentrations of diamine oxidase (DAO) and fatty acid-binding protein 2 (FABP2) in the serum and the concentration of TNF-αand IL-6 in the tissues were measured .RESULTS:Compared with sham group , the intestinal mucosa of the rats showed obvious pathological injury after liver reperfusion in OALT group and ROS group , the Chiu’s scores of intestinal mucosa was signifi-cantly higher , and the serum concentrations of DAO and FABP 2 increased ( P<0.05 ) .After rosiglitazone pretreatment , the injury of intestinal mucosa of the rats was alleviated , the Chiu’s scores was lower and the serum concentrations of DAO and FABP2 decreased (P<0.05), the PPARγexpression was obviously up-regulated in the intestinal tissues, the nuclear translocation of NF-κB was reduced and the concentrations of IL-6 and TNF-αwere decreased .CONCLUSION: During perioperative period of OALT in rats , the inflammatory responses are obvious .Furthermore, obvious intestinal injury oc-curs .PPARγagonist rosiglitazone obviously up-regulates PPARγexpression and inhibits the inflammation in the intestines , thus protecting against intestinal injury in rats undergoing OALT .
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Objective To evaluate the changes in the expression of small intestinal thioredoxin 2 (Trx2) during different periods after orthotopic liver autotransplantation (OLAT) in rats.Methods Forty Sprague-Dawley rats,aged 8-10 weeks,weighing 210-260 g,were randomly divided into 2 groups using a random number table:sham operation group (group S,n =8) and OLAT group (n =32).Intestinal tissues were removed at 4,8,16 and 24 h after OLAT for microscopic examination and for determination of the levels of superoxide anion (O2--),hydrogen peroxide (H2 O2),glutathione peroxidase (GSH-Px),reduced glutathione (GSH) and Trx2.Intestinal damage was assessed and scored according to Chiu.Results Compared with S group,the Chiu's score and O2--activity at 4,8 and 16 h after OLAT and H2O2 content at 4 and 8 h after OLAT were significantly increased,and the levels of GSH-Px and GSH and expression of Trx2 at 4 and 8 h after OLAT were decreased in OLAT group (P ＜ 0.05).Chiu' s score at 4,16 and 24 h after OLAT and H2O2 content at 16 and 24 h after OLAT were significantly lower than those at 8 h in OLAT group (P ＜ 0.05).Conclusion The rats undergo decreased antioxidant capacity in the early phase and recovery in the late phase mediated by small intestinal Trx2 after OLAT.
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Objective To investigate the difference of neuromuscular blocking effect of cis-atracurium under sevoflurane anesthesia between the genders. Methods 30 ASA Ⅰ or Ⅱ patients aged from 18 to 45 years who scheduled for laparoscopic operation were divided into two groups, male group( M group, n = 15 ) and female group ( F group,n = 15). After induction of Anesthesia all cases were maintained with remifentanyl 3μg/L(TCI) and sevoflurane.After 40 minutes of stable end-tidal anaesthetic concentration, a total dose of cisatracurium 45 μg/kg was divided into 3 equal doses( 15μ g/kg each) ,which was administered accumulatively in each patient. The next dose was given when the effect of the previous dose had reached its peak ( T1 was no longer depressed in the height of 3 successive stimuli).Neuromuscular block was monitored using accelograph(TOF GUARD,Denmark). The onset time and maximum depression of T1 of the initial dose and 2 incremental doses were recorded. The cumulative dose-response curves of the two groups were established. The effective dose to obtain 50% and 95% neuromuscular block( ED5o and ED95 ,respectively) were calculated from individual dose-response curves. After the lastincrement of 15 μg/kg, the time for T1 to return to 25% ,50% ,75% and TOF ratio(T4/T1 )to 70% were recorded. The recovery index( RI)was also calculated.Results The mean ED5o and ED95(95% confidence interval)of cisatracurium of women were 22.2( 15.8 ～27.2)and 38.4 ( 32.1 ～ 54.4) μg/kg during sevoflurane (1.3MAC) anaesthesia, while the data of men were 25.6 ( 19.7 ～30.8) μg/kg and 42.8 ( 36.3 ～ 58.2 ) μg/kg, the difference between groups had no statistical significance ( P ＞0. 05). There was no significant difference in the TOF ratio ( T4/T1 ) to 70% and recovery index between the two groups( P ＞0.05 ). The onset time of F group was shorter than M group. The time for T1 to return to 25% ,50% and TOFR 0.7 was significantly longer in the F group than in the M group (P ＜ 0.05). Conclusion The neuromuscular blocking effect of cis-atracurium under 1.3MAC sevoflurane anesthesia remained no difference between genders. But the onset time of women was much faster. Furthermore the effect on the time for T1 to return to 25% ,50% and TOFR 0.7 were greater than men.
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Objectlve investigate the role of Toll-like receptor 2 (TLR2) on polymorphonuclear neutrophil (PMN) during perioperative period in the development of postoperative systemic inflammatory response syndrome (SIRS) in patients undergoing orthotopic liver transplantation (OLT).Methods Twenty patients (18 male and 2 female, aged 33-58 yr and weighing 52-73 kg) with ASA Ⅲ or Ⅳ (NYHA Ⅱ or Ⅲ )undergoing OLT were studied. Blood samples were collected from the central vein for determination of TLR2 expression on PMN and plasma TNF-α, IL-1β and IL-8 concentrations before induction of anesthesia (T1, baseline), at 25 min of anhepatic phase (T2), 3 h (T3) and 24 h after beginning of reperfusion of the allograft (T4). The expression of TLR2 was measured by flow cytometry and the serum concentrations of TNF-α, IL-1β and IL-8 were measured by enzyme linked immunosorbant assay (ELISA). The patients were divided into SIRS and non-SIRS group depending on whether the patients developed SIRS or not within 7 days after operation. The diagnosis of SIRS was based on the criteria laid down by ACCP and SCCM in 1992.Results Ten patients developed SIRS within 7 days after operation. There was no significant difference in Child-Turcotte-Pugh (CTP) scores between the two groups. Compared with non-SIRS group, the TLR2 expression on PMN and the serum IL-1β concentration were significantly increased at T4 and the serum IL-8 concentration was significantly increased at T3 in SIRS group.There was positive correlation between serum TNF-α concentration and TLR2 expression on PMN in SIRS group ( r= 0.607, P ＜0.05).Conclusion The expression of TLR2 on PMN increases significantly at 24 h after beginning of reperfusion of allograft and may play an important role in the development of postoperative SIRS.
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In order to successfully develop the effective population pharmacokinetic model to predict the concentration of propofol administrated intravenously, the data including the concentrations across both distribution and elimination phases from five hospitals were analyzed using nonlinear mixed effect model (NONMEM). Three-compartment pharmacokinetic model was applied while the exponential model was used to describe the inter-individual variability and constant coefficient model to the intra-individual variability, accordingly. Covariate effect including the body weight on the parameter CL, V1, Q2, V2, Q3 and V3 were investigated. The performance of final model was assessed by Bootstrapping, goodness-of-fit and visual predictive checking (VPC). The context-sensitive half-times and the infusion rates necessary to maintain the concentration of 1 microg x mL(-1) were simulated to six subpopulations. The results were as follows: the typical value of CL, V1, Q2, V2, Q3 and V3 were 0.965 x (1 + 0.401 x VESS) x (BW/59)(0.578) L x min(-1), 13.4 x (AGE/45)(-0.317) L, 0.659 x (1 + GENDER x 0.385) L x min(-1), 28.8 L, 0.575 x (1 + GENDER x 0.367) x (1 - 0.369 x VESS) L x min(-1) and 196 L respectively. Coefficients of the inter-individual variability of CL, V1, Q2, V2, Q3 and V3 were 29.2%, 46.9%, 35.2%, 40.4%, 67.0% and 49.9% respectively, and the coefficients of residual variability were 24.7%, 16.1% and 22.5%, the final model indicated a positive influence of a body weight on CL, and also that a negative correlation of age with V1. Q2 and Q3 in males were higher than those in females at 38.5% and 36.7%. The CL and Q3 were 40.1% increased and 36.9% decreased in arterial samples compared to those in venous samples. The determination coefficient of observations (DV)-individual predicted value (IPRED) by the final model was 0.91 which could predict the propofol concentration fairly well. The stability and the predictive performance were accepted by Bootstrapping, the goodness-of-fit and VPC. The context-sensitive half-times and infusion rates necessary to maintain the concentration of 1 microg x mL(-1) were different obviously among the 6 sub-populations obviously. The three-compartment model with first-order elimination could describe the pharmacokinetics of propofol fairly well. The involved fixed effects are age, body weight, gender and sampling site. The simulations in 6 subpopulations were available in clinical anesthesia. The propofol anesthesia monitor care could be improved by individualization of pharmacokinetic parameter estimated from the final model.
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Objective To investigate the changes in systemic and pulmonary hemodynamics in patients with liver cirrhosis and portopulmonary hypertension(PPH)during liver transplantation.Methods Eight patients with liver cirrhosis and PPH(5 male,3 female)aged 50-63 yr weighing 45-80 kg were included in PPH group. Another 8 liver-cirrhotic patients without PPH served as control group.The patients were premedicated with intramuscular phenobarbital 0.1 g and atropine 0.5 mg.Anesthesia was induced with midazolam 3-5 mg,fentanyl 0.15-0.2 mg,propefol 1 mg?kg~(-1) and vecuronium 0.1 mg?kg~(-1) and maintained with 0.5%-3% isoflurane inhalation and intermittent Ⅳ boluses of fentanyl and vecuronium.The patients were mechanically ventilated after tracheal intubation.P_(ET)CO_2 was maintained at 30-45 mm Hg.Right subclavian vein was cannulated for fluid and drug administration and blood transfusion.Radial artery was cannulated for BP monitoring.Swan-Ganz catheter was placed via right internal jugular vein.BP,CVP,MPAP,PAWP,CI,PVRI and SVRI were monitored and recorded before operation(baseline),during preanhepatic phase,at 3 and 30 min of anhepatic phase and 3,7, 15,60 min of neohepatic phase and at the end of operation.Results(1)The two groups were comparable with respect to fluid balance,the amount of vasoactive drugs used during anhepatic and neohepatic phase,duration of anhepatic phase and operation.(2)MPAP and PVRI were significantly higher before operation in PPH group than in control group.(3)CI,MPAP, PAWP and CVP were siguificanfly decreased during anhepatic phase as compared to the baseline values(before operation)in both groups and then gradually returned to and even exceeded the baseline values during neohepatic phase.(4)During neohepatic phase PVRI in PPH group was significantly increased as compared to the baseline value and was significantly higher than that in control group.Conclusion MPAP and PVRI are significantly increased during neohepatic phase in patients with PPH and need to be treated.