Objective To investigate the effect of ondansetron on the analgesic efficacy of tramadol for postoperative patient-controlled intravenous analgesia (PCIA). Methods Forty ASA I - II patients aged 22-74 years, weighing 40-90 kg scheduled for radical mastectomy were randomly allocated to one of two groups : control group ( n = 20) and ondansetron group ( n = 20) . The patients were premedicated with intramuscular atropine 0.01 mg?kg-1 and diazepam 0.2 mg?kg-1. Anesthesia was induced with midazolam 0.1-0.2 mg (total dose was limited to 15 mg), fentanyl 2.4?g?kg-1 , propofol 1.5-2.0 mg?kg-1 and vecuronium 0.12-0.15 mg?kg-1 . The patients were mechanically ventilated after tracheal intubation (VT 8-10 ml?kg-1 , RR 13 bpm). Anesthesia was maintained with enflurane inhalation and continuous infusion of vecuronium. The patients were attached to a PCIA pump after operation and received PCIA with 1 % tramadol (background infusion 2 ml?h-1 , bolus dose 2 ml, lockout interval 10min) in both groups. In ondansetron group the patients received ondansetron 6 mg iv during operation and a loading dose of tramadol 1 mg?kg-1 and ondansetron 2 mg after operation before PCIA. Pain score (VAS 0-10), sedation score (0-3), tramadol consumption and the incidence of nausea and vomiting were recorded at 4, 8, 12 and 24 h after operation. Results There was no significant difference in pain and sedation scores and the incidence of vomiting between the two groups. Significantly more tramadol was consumed at 4, 8 and 12 h after operation in the ondansetron group as compared with control group (P

Objective To evaluate the efficacy of nalmefene in preventing sufentanil-induced cough during induction of general anesthesia.Methods One hundred American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes,aged 21-62 yr,weighing 45-82 kg,undergoing elective laparoscopic cholecystectomy under general anesthesia,were divided into 2 groups (n =50 each) using a random number table:nalmefene group (group N) and control group (group C).Nalmefene 0.25 μg/kg was injected intravenously at 2 min before anesthesia induction in group N,and the equal volume of normal saline was given instead in group C.Anesthesia was induced with target-controlled infusion of propofol,and sufentanil 0.5 μg/kg was injected over 5 s when bispectral index value reached 55.The number of patients who developed cough within 2 min after sufentanil injection and severity of cough were observed.Other iv anesthetics were given for induction after the end of observation.Results The incidence of sufentanil-induced cough was 8％ in group N and 48％ in group C.Compared with group C,the incidence and severity of cough were significantly decreased in group N (P＜0.05).Conclusion Nalmefene 0.25 μg/kg injected at 2 min before induction of anesthesia can effectively decrease the development of sufentanil-induced cough during induction of general anesthesia.

ObjectiveTo compare the roles of Toll-like receptor-4 (TLR-4) in the acute lung injury (ALI) induced by lipopolysaccharide (LPS) and by hemorrhagic shock and resuscitation (HSR) and LPS (twohit) in mice.MethodsTwo types of mice were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type ( C3H/HeJ).Each type of mice was randomly divided into 2 groups ( n ＝ 18):group sham operation+ LPS (group S/LPS) and group HSR + LPS (group HSR/LPS).Hemorrhagic shock was induced by blood withdrawal until MAP was reduced to 35-45 ram Hg and maintained for 60 min (first hit).The animals were then resuscitated by infusion of shed blood and lactated Ringer' s solution.LPS 30 tμg/kg was instilled into trachea at 24 h after HSR (second hit).Arterial blood gas analysis was performed and the animals were then sacrificed by exsanguination at 0,3 and 6 h after LPS(T,,T2,T3 ).The lungs were removed.W/D lung weight ratio and MPO activity,IL-6 and 1L-10 contents in the lung tissue were determined.The changing rate of the abovementioned variables at T2,T3 based on the values at T1 were calculated.ResultsIn C3H/HeN animals the changing rate of PaO2 was significantly lower while the changing rate of W/D ratio,MPO activity and IL-6,IL-10 contents in the lung tissue were significantly higher in HSR/LPS group than in S/LPS group at T2.3.But in C3H/HeJ animals the above-mentioned variables were changed at T2.ConclusionThe role of TLR-4 in the two-hit-induced ALI is stronger than that in the LPS-induced ALI in mice.

Objective To investigate the effect of Shenfu injection (SFI) on hypoxia and reoxygenation (H/R)-induced apoptosis and the expression of Bcl-2 and Caspase-3 in cultured neonatal rat cardiomyocytes and to explore the possible molecular protective mechanisms of SFI from hypoxia and reoxygenation injury in cardiacmy-ocytes in vitro. Method The experiment was performed in Research Center for Cardiovascular Regenerative Medicine, Cardiovascular Institute and Fuwai Hospital in Beijing. Ventricular myocytes from the hearts of neonatal Sprague-Dawley rats (1- to 2-day old) were cultured. The model of hypoxia and reoxygenation injury was devel-oped in primary cultured neonatal rat cardiacmyocytes. The cultured cells were randomly divided into four groups: (1) Control group (Con group), without any treatment; (2) Hypoxia and Reoxygenation group (H/R group),4 h hypoxia followed by 16 h reoxygenation; (3) Low-dose SFI group (L-SFI group),cardiacmyocytes were pretreated with a low dose (50 μL/mL) of SFI for 30 min followed by H/R; (4) High-dose SFI group (H-SFI group),car-diacmyocytes were pretreated with a high dose (100 μL/mL) of SFI for 30 min followed by H/R. Apoptosis was quantified by fluoreacence-activated cell sorter (FACS) analysis after staining with Fluorescein isothiocyanate (FITC)-labled Annexin-V (Annexin V-FITC) and propidine iodide (PI). The expressions of Bcl-2 and Caspase-3 were detected by ECL-Western blot analysis. All data are expressed as mean±S.E.M. One-way analysis of vari-ance (ANOVA) was performed followed by Student-Newman-Keul test using SSPS 11.5 software. A p value less than 0.05 were considered as statistically significant. Results The results of FACS analysis indicated that the rate of different apoptotic process in cardiomyocytes was significantly increased after H/R, while after SFI treatment the occurrence of cell apoptosis induced by H/R was decreased significantly. The results of ECL-Western blot analysis showed that cells' exposure to H/R induced proteolytic cleavage of caspases,as revealed by the appearance of the characteristic fragment at 17 000 of Caspase-3 and this proteolytic activation was nearly completed with difference concentration SFI incubation. The anti-apoptotic protein Bcl-2 in cardiomyocytes was decreased after H/R insult and was increased in cells with SFI pretreatment. Conclusions SFI has protective effects on cardiacmyocytes a-gainst apoptosis that could be induced by H/R injury, the mechanisms of which probably involve the inhibition of down-regulation of Bcl-2 protein level and sequential activation of Caspase-3.

Objective To evaluate the role of μ opioid receptor exon 7 in the analgesic efficacy of endomorphin-2 in rats.Methods Twenty-four male Sprague-Dawley rats in which IT catheters were successfully implanted,weighing 220-260 g,were randomly divided into 3 groups (n =8 each) using a random number table:normal saline control group (group C),negative siRNA control group (group N-siRNA) andμ opioid receptor exon 7 siRNA group (group E7-siRNA).In C,N-siRNA and E7-siRNA groups,30μl saline solution,negative siRNA plasmid 20 μl + lipofectamine 2000 (10 μl),and μ opioid receptor siRNA plasmid 20μ1 + lipofectamine 2000 (10 μl) were intrathecally injected once a day for 3 consecutive days.The mechanical pain threshold was measured on 4th day (baseline).Endomorphin-2 10 μg was injected intrathecally at 1 h after measurement of the pain threshold.The mechanical pain threshold was measured at 5,20,40 and 60 min after endomorphin-2 injection,and the analgesic efficacy was calculated.Results There was no significant difference in the baseline pain threshold among the three groups.Compared with group C,no significant difference was found in the analgesic efficacy at each time point after endomorphin-2 injection in group N-siRNA,and the analgesic efficacy was significantly decreased at 5 and 20 min after endomorphin-2 injection in group E7-siRNA.Conclusion μ opioid receptor exon 7 is involved in the analgesic efficacy of endomorphin-2 in rats.

Objective To investigate the effect of electro-acupunctare at zusanli on acute lung injury in a rat model of sepsis after scald.Methods Fifty SPF male Sprague-Dawley rats,weighing 200-250 g,aged 2-3 months,were randomly divided into 5 groups (n =10 each) using a random number table:control group (group C),sepsis after scald group (group SS),electro-acupuncture at zusanli group (group E),electric stimulation of non-acupoint group (group NE) and electro-acupuncture at zusanli + α-bungarotoxin (α-BGT,a selective α7 nicotinic acetylcholine receptor antagonist) group (group α-BGT).The rats were subjected to a third degree scald covering 20％ total body surface (TBS) and muramyl dipeptide (MDP) 5 mg/kg was injected into the femoral vein immediately after scald to induce sepsis.Electro-stimulation (3 V,2 ms,3 Hz) of bilateral zusanli was performed for 12 min starting from the time point immediately after MDP injection and every 8 h for 2 consecutive days in group E.In group NE,electro-stimulation was performed at the points 5 mm lateral to the bilateral acupoints of Zusanli and the method was similar to those previously described in group E.In group α-BGT,α-BGT 1.0 μg/kg (in 1 ml of normal saline) was injected into the femoral vein before electro-stimulation of zusanli.At 48 h after treatment,arterial blood samples were obtained for determination of serum tumor necrosis factor-alpha (TNF-α) and high mobility group box-1 (HMGB1) protein levels (by ELISA) and lung specimens were removed for microscopic examination and for determination of the expression of Nod like receptor 2 (NLR2) mRNA (by RT-PCR) and receptor interacting protein 2 (RIP2) in the lung tissues (by Western blot).Results Compared with group C,the expression of NLR2 mRNA and RIP2 was significantly up-regulated,and the serum TNF-α and HMGB1 levels were increased in SS,NE and α-BGT groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group E (P ＞ 0.05).Compared with group SS,the expression of NLR2 mRNA and RIP2 was down-regulated,and the serum TNF-α and HMGB1 levels were decreased in group E (P ＜ 0.05),and no significant change was found in the parameters mentioned above in NE and α-BGT groups (P ＞ 0.05).Compared with group E,the expression of NLR2 mRNA and RIP2 was significantly up-regulated,and the serum TNF-α and HMGB1 levels were increased in NE and α-BGT groups (P ＜ 0.05).The pathological changes of lung tissues were significantly reduced in group E as compared with group SS.Conclusion Electro-acupunctare at Zusanli can reduce acute lung injury in a rat model of sepsis after scald and inhibition of NLR2/RIP2 signaling pathway and activation of cholinergic anti-inflammatory pathway in lung tissues may be involved in the mechanism.

Objective To investigate the effects of penehyclidine hydrochloride ( PHC) on lipopolysaccharide (LPS) -induced endothelial cells injury and its mechanism. Methods ECV-304 was cultured in RPMI1640 in a 5% humidified CO2 atmosphere at 37 ℃. Then cultured cells were used to assess the following treatments: control group, LPS group (1 μg/mL) and PHC group(2 μg/mL). At the end of the experiments, supernatant was collected for determination of lactate dehydrogenase ( LDH), and cells were collected for determination of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. And extracellular regulated kinasel/2( ERKl/2)and JNK MAPK (mitogen-activated protein kinases, MAPK) protein expressions were determined using Western blot technique. Analysis of variance (ANOVA) was used for statistical analysis to compare values among all groups. A significant difference was presumed for a probability value < 0.05. Results Compared with control group, LDH leakage [(1642 ± 367) U/L vs (169±33)U/L], the contents of MDA[(13. 2 ± 1. 2) nmol/L vs (7. 2 ±0. 8)nmol/mL] and NO levels [(143.2 ± 10.3) μmol/L vs(85.5 ±4.1) μmol/L], expressions of ERK1/2 and JNK were remarkably increased and SOD activities[(41.2 ±2.7) U/mL vs (61. 1 ±2.8) U/mL] were obviously decreased in LPS group. PHC markedly decreased LDH leakage [(392 ±90) U/L], MDA contents [(8. 6 ± 1. 3) nmol/ mL] and NO levels [(92.1 ±6.6) μmol/L], ERK1/2 activation and enhanced SOD activities [(58.0± 3.0) U/mL]. Conclusions PHC could protect endothelial cells against LPS-induced cell injury. The effect of PHC is likely mediated through inhibition of ERK1/2 MAPK activation.

ObjectiveTo investigate the effect of flurbiprofen axetil on lung ischemia-reperfusion(I/R) injury in rats.MethodsSixty healthy male SD rats weighing 250-300 g were randomly divided into 3 groups( n =20 each): group sham operation(group S) ;group I/R and group flurbiprofen axetil (group FA).The animals were anesthetized with intraperitoneal 2％ pentobarbital 50 mg/kg and tracheostomized and mechanically ventilated.Lung I/R was induced by 60 min occlusion of left hilus pulmonis followed by 120 min reperfusion.In FA group flurbiprofen axetil 10 mg/kg was injected iv at 15 min before occlusion of left hilus pulmonis.The rats were sacrificed at 120 min of reperfusion and then the lungs were removed for measurement of lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and microscopic examination.Bcl-2/Bax ratio was caculated.ResultsI/R significantly increased lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and decreased Bcl-2/Bax ratio.Flurbiprofen axetil preconditioning significantly attenuated the I/R-induced changes in lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and Bcl-2/Bax ratio in group FA as compared with group I/R.Flurbiprofen axetil preconditioning also ameliorated I/R-induced lung damage.ConclusionFlurbiprofen axetil can attenuate lung I/R injury in rats by inhibiting NF-κB activity,up-regulating Bcl-2 expression and down-regulating Bax expression and inhibiting apoptosis.

Objective To evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 (HO-1) expression during hemorrhagic shock and resuscitation (HSR)-induced acute lung injury (ALI) in mice. Methods Thirty-two C3H/HeN (wild-type) mice, aged 10-12 weeks, weighing 20-25 g, were randomly divided into 4 groups (n = 8 each): sham operation group (group S); group HSR; FR167653 (a p38MAPK inhibitor) group (group FR) and FR167653 + HSR group (group FR + HSR). HSR was induced according to the methods described by Ayala et al. MAP was reduced to 35-45 mm Hg and maintained for 60 min.Then the animals were resuscitated with transfusion of the shed blood and lactated Ringer's solution equivalent to the volume of shed blood. FR167653 5 mg/kg was injected intravenosly in group FR. FR167653 5 mg/kg was injected intravenously 30 min before blood-letting in group FR + HSR. The animals were sacrificed by exsanguination at 6 h after resuscitation. The lungs were immediately removed for microscopic examination. The W/D lung weight ratio was calculated and the levels of myeloperoxidase (MPO), IL-10, IL-6 and HO-1 and activated p38MAPK were determined (by ELISA).Results Compared with group S, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and the level of activated p38MAPK were significantly increased in group HSR, the pathological score, W/D ratio and the level of HO-1 were significantly increased in group HSR + FR ( P ＜ 0.01) .Compared with group HSR, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and activated p38MAPK were significantly decreased in group HSR + FR ( P ＜ 0.01 ). Conclusion p38MAPK signaling pathway mediates the up-regulation of HO-1 expression during HSR-induced ALI in mice.

Objective To investigate the effects of flurbiprofen pretreatment on the permeability of bloodbrain barrier in a rat model of global cerbral ischemia-reperfusion (I/R) injury. Methods Forty-five male SD rats weighing 300-350 g were randomly divided into 3 groups (n = 15 each): sham operation group (group S); global cerebral I/R group (group I/R); flurbiprofen 10 mg/kg + global cerebral I/R group (group F). Global cerebral ischemia was induced by 20 min occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mm Hg). In group F, flurbiprofen 10 mg/kg was injected iv at 15 min before ischemia. Evans blue 3 ml/kg was injectcd iv at 24 h of reperfusion, then the rats were sacrificed and their brains were immediately removed for determination of the apoptosis rate, brain water content, Evans blue content, TNF-α, IL-1β and IL-10 content, and microscopic examination. Results The apoptosis rate, brain water content, Evans blue content, and TNF-α, IL-1β and IL-10 content were significantly higher in group I/R and F than in group S (P ＜ 0.05 or 0.01).The apoptosis rate, brain water content, and Evans blue content and TNF-α and IL-1β content were significantly lower, while IL-10 content was higher in group F than in group I/R (P ＜ 0.01). Global cerbral I/R-induced changes were significantly attenuated in group F. Conclusion Pretreatment with flurbiprofen can protect bloodbrain barrier against cerebral I/R injury by inhibition of the inflammatory reaction.