Objective To evaluate the role of protein kinase Cα( PKCα)?nuclear factor E2?related factor 2 ( Nrf2)?heme oxygenase?1 ( HO?1) signaling pathway on endotoxic shock?induced acute lung injury ( ALI) in rabbits. Methods Thirty healthy male New Zealand white rabbits, aged 2 months, weighing 2?0-2?5 kg, were randomly divided into 3 groups ( n=10 each) using a random number table: normal control group ( group C);ALI group ( group ALI);PKCα inhibitor chelerythrine group ( group CHE) . In group CHE, chelerythrine 8 mg∕kg ( in 0?5 ml of DMSO) was injected intraperitoneally, and 30 min later, LPS 5 mg∕kg ( in 2 ml of normal saline) was injected via the auricular vein to induce ALI in ALI and CHE groups. The rabbits were then sacrificed at 6 h after injection of LPS or normal saline, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet∕dry lung weight ratio ( W∕D ratio) , and the expression of Nrf2 and HO?1 protein and mRNA. Results Compared with group C, the pathological score and W∕D ratio were significantly increased, and the expression of Nrf2 and HO?1 protein and mRNA was up?regulated in ALI and CHE groups. The pathological score and W∕D ratio were significantly higher, and the expression of Nrf2 and HO?1 protein and mRNA was lower in group CHE than in group ALI. Conclusion The PKCα?Nrf2?HO?1 signaling pathway is one of the endogenous protective mechanisms underlying endotoxic shock?induced ALI in rabbits.

Objective To evaluate the myocardial protective effect of dexmedetomidine during non-cardiac surgery in patients with coronary heart disease.Methods Eighty ASAⅡor Ⅲ patients with coronary heat disease (NYHA Ⅱ or Ⅲ)aged 43-76 yr weighing 52-80 kg scheduled for elective upper abdominal surgery were randomly divided into 2 groups(n=40 each)：control group(group C)and dexmedetomidine group(group D).Anesthesia was induced with etomidate 0.25 mg／kg，sufentanil 0.5 μg／kg and vecuronium 0.1 mg／kg.The patients were tracheal intubated and mechanically ventilated.A loading dose of dexmedetomidine 1μg/kg was injected intravenously 10 min before induction followed by infusion at 0.4 μg·kg-1·h-1 until the end of operation in group D.While equal volume of normal saline was given in group C.BIS was maintained at 40-49.Blood samples were taken before induction and at the end of operation for determination of serum concenlrations of IL-6，TNF-α，cardiac troponin Ⅰ(cTnI)and glycogen phosphorylase BB(GP-BB).The adverse cardiovascular events were recorded during operation.Results The serum concentrations of IL-6，TNF-α，cTnI and GP-BB and incidences of tachycardia and myocardial ischemia were significantly lower，while the incidences of bradycardia highcr in group D than in group C (P<0.05).Conclusion Dexmedetomidine Can exert the myocardial protective effect during non-cardiac surgery in patients with coronary heart disease and the mechanism may be related to the inhibition of the release of pro-inflammatory cytokines.

Objective To investigate the effect of electro-acupuncture (EA) on nuclear factor E2-related factor 2 (Nrf2) expression in the renal tissues of rabbits with endotoxic shock-induced acute kidney injury (AKI) and the relationship with p38 mitogen-activated protein kinase (p38MAPK) signaling pathway.Methods Seventy male New Zealand white rabbits,weighing 1.5-2.0 kg,aged 2 months,were randomized into 7 groups (n =10 each) using a random number table:normal control group (C group),endotoxic shock-induced AKI group (AKI group),EA + endotoxic shock-induced AKI group (EA group),non-acupoints + endotoxic shock-induced AKI group (SA group),EA + endotoxic shock-induced AKI + specific p38MAPK blocker SB203580 group (EAS group),SB203580 group (S group),and ethanol group (A group).EA (intensity 1-2 mA,frequency 2/100 Hz,wave length 0.2-0.6 ms) of Zusanli and Shenyu lasting for 15 min was performed once a day for 5 consecutive days in EA and EAS groups.In SA group,EA was performed at the points 0.5 cm lateral to the acupoints of bilateral Zusanli and Shenyu using the parameters of EA mentioned above.At 24 h after the last EA,endotoxic shock-induced AKI was induced by injection of lipopolysaccharide (LPS) 5 mg/kg (in 2 ml normal saline) in AKI,EA,SA and EAS groups,while the equal volume of normal saline was given in the other groups.At 30 min before the model was established,5/μmol/kg SB203580 (in 0.5 ml ethanol) was injected intravenously in EAS and S groups,while ethanol 0.5 ml was given in A group and the equal volume of normal saline was given in the other groups.Blood samples were obtained at 6 h after administration of LPS or normal saline for determination of serum urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were sacrificed and kidney specimens were obtained for microscopic examination of pathological changes which were scored and for measurement of Nrf2 protein expression and phosphorylation of p38MAPK (by Western blot) and Nrf2 mRNA expression (using fluorescent quantitative PCR).Results Compared with C group,the pathological score and serum BUN and Cr concentrations were significantly increased,and Nrf2 mRNA and protein expression was up-regulated in AKI,EA,SA and EAS groups,the phosphorylation of p38MAPK was increased in AKI,EA and SA groups,and no significant changes were found in the parameters mentioned above in S and A groups.Compared with AKI group,the pathological score and serum BUN and Cr concentrations were significantly decreased,and Nrf2 mRNA and protein expression was up-regulated in EA and EAS groups,the phosphorylation of p38MAPK was increased in EA group,the phosphorylation of p38MAPK was decreased in EAS group,and no significant changes were found in the parameters mentioned above in SA group.Compared with EA group,the pathological score and serum BUN and Cr concentrations were significantly increased,Nrf2 mRNA and protein expression was down-regulated,and the phosphorylation of p38MAPK was decreased in EAS group.Conclusion The mechanism by which EA mitigates endotoxic shock-induced AKI may be related to activation of p38MAPK signaling pathway and up-regulation of Nrf2 expression in renal tissues of rabbits.

Objective To investigate the awaken effect of naloxon on dexmedetomidine anesthetized mice and its mechanism. Methods Thirty Kunming mice of clean grade were randomly divided into 3 groups which included NAL group (Naloxon group), ATI group(Atipamezole group)and NS group (Normal Saline group). All groups were given dexme?detomidine 1 mg·kg-1 intraperitoneally. Naloxon 2 mg·kg-1, atipamezole 2 mg·kg-1 and normal saline 10 mL·kg-1 were ran?domly given intraperitoneally to the NAL, ATI and NS group respectively 90 minutes after dexmedetomidine administration. At timepoints prior to dexmedetomidine administration and 5, 15, 30, 60, 90, 95, 105, 120, 180 minutes after it, the sedative and analgesic effects besides recovery time (based on restore of righting reflex loss) were assessed. Results Sedation and analgesia effects became apparent within 5 minutes, and peaked at approximately 60 minutes then spontaneously recovered at 180 minutes after injection of dexmedetomidine. The sedative and analgesic effects were reduced in both ATI and NAL groups. Compared with ATI group, the sedation scores were higher at 95, 105 and 120 minutes after dexmedetomidine admin?istration than those in NAL group (P<0.05) but the scores were not statistically significant at 180 minutes between these two groups. Compared with NS group, the sedation scores were lower at time points of 95, 105, 120 and 180 minutes than those in NAL group (P>0.05). The analgesic scores were not statistically significant at time points of 95, 105, 120 and 180 min?utes between NAL group and ATI group, but they were lower in NAL group compared with NS group at timepoints of 95, 105 and 120 minutes (P>0.05). The recovery time in ATI and NAL group were shorter than that in NS group (F=1 793.368, P<0.05), but it showed no statistical difference between ATI group and NAL group (P>0.05). Conclusion Naloxone had a certain awaken effect on dexmedetomidine anesthetized mice.

Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway in endotoxic shock-induced acute lung injury (ALI) in rabbits.Methods Thirty healthy male New Zealand white rabbits, aged 2 months, weighing 1.5-2.0 kg, were randomly divided into 3 groups (n =10 each) using a random number table: control group (group C), ALI group, and wortmannin group (group W).In group W, wortmannin 0.6 mg/kg (in 0.08 ml/kg dimethyl sulfoxide) was injected via the auricular vein, while the equal volume of normal saline was given in C and ALI groups.And 30 min later, lipopolysaccharide (LPS) 5 mg/kg (in 2 ml of normal saline) was injected via the auricular vein in ALI and W groups, while the equal volume of normal saline was given in group C.The rabbits were sacrificed at 6 h after LPS or normal saline injection.The lung was immediately removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio), expression of phosphorylated Akt (p-Akt) , Nrf2 and heme oxygenase-1 (HO-1) (by Western blot), and expression of Nrf2 and HO-1 mRNA (using fluorescent quantitative real-time reverse transcriptase-polymerase chain reaction).The pathological changes of the lung were scored.Results Compared with group C, the lung injury scores and W/D ratio were significantly increased, and the expression of p-Akt, Nrf2 protein and mRNA, and HO-1 protein and mRNA was up-regulated in ALI and W groups (P＜0.05).Compared with group ALI, the lung injury scores and W/D ratio were significantly increased,and the expression of p-Akt, Nrf2 protein and mRNA, and HO-1 protein and mRNA was up-regulated in group W (P＜0.05).Conclusion Activation of PI3K/Akt/Nrf2 pathway is the regulatory mechanism of the body adapting to the development of endotoxic shock-induced ALI in rabbits.

Objective To evaluate the role of activator protein-1 (AP-1 ) in electro-acupuncture (EA )-induced up-regulation of heme oxygenase-1 (HO-1 ) expression in lung tissues in a rabbit model of endotoxic shock .Methods Seventy healthy male New Zealand white rabbits ,aged 2 months ,weighing 1.5-2.0 kg ,were randomly divided into 7 groups ( n=10 each ) using a random number table :normal control group (group C ) , endotoxic shock-induced acute lung injury (ALI ) group (group ALI ) , EA + ALI group (group EL ) , non-acupoint+EA+ ALI group (group NEL ) , curcumin (HO-1 inhibitor ) group (group Cur ) , dimethyl sulfoxide group (group D ) ,and EA+ALI+curcumin group (group ELC ) .Bilateral 15 min EA stimulation of Zusanli and Feishu (according to atlas of animals acupoints ) was performed (frequency 15Hz ) once a day for 5 consecutive days before lipopolysaccharide (LPS ) administration in EL and ELC groups ,while in group NEL ,EA stimulation was performed at non-acupoints located 0.5 cm lateral to Zusanli and Feishu acupoints with the same parameters . The animals were anesthetized with urethane and tracheostomized .The animals kept spontaneous breathing .Right internal carotid artery was cannulated for blood pressure monitoring . Ear vein was cannulated for drug administration .At 5 days after EA stimulation ,curcumin 25 mg/kg (in 0.5 ml of 0.1% dimethyl sulfoxide ) was injected in Cur and ELC groups ,0.1% dimethyl sulfoxide 0.5 ml was injected in D group ,and the equal volume of normal saline was given in the other groups .LPS 5 mg/kg (in 2 ml of 0.9% normal saline ) was injected intravenously at 30 min after administration in ALI ,EL ,NEL and ELC groups ,while the equal volume of normal saline was given in the other three groups .Endotoxic shock was confirmed by decrease in mean arterial pressure to 75% of the baseline value within 2 h after LPS injection .Blood samples were collected from the common carotid artery at 6 h after LPS or normal saline administration and the rabbits were then sacrificed .The lungs were removed for microscopic examination and the pathological changes were scored .The wet/dry lung weight ratio (W/D ratio ) was calculated .The malondialdehyde (MDA ) content and superoxide dismutase (SOD ) activity in lung tissues were detected ,and the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun in lung tissues was determined by Western blot .Results Compared with group C ,the pathological score ,W/D ratio and MDA content were significantly increased ,and the SOD activity was decreased in ALI ,EL ,NEL and ELC groups ,the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun was up-regulated in groups ALI ,EL and NEL ( P<0.05 ) ,while no significant change was found in the expression of c-Jun mRNA and c-Jun in group ELC ( P>0.05) .There was no significant difference in the parameters mentioned above between Cur and D groups ( P>0.05 ) .Compared with group ALI ,the pathological score ,W/D ratio and MDA content were significantly decreased ,and SOD activity was increased ,and the expression of HO-1 mRNA and HO-1 was up-regulated in EL and ELC groups ( P<0.05) ,the expression of c-Jun mRNA and c-Jun was up-regulated in group EL ,while down-regulated in group ELC ( P<0.05) ,and no significant change was found in the parameters mentioned above in group NEL ( P>0.05) .The pathological score ,W/D ratio and MDA content were significantly higher ,and the SOD activity and expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun were lower in group ELC than in group EL ( P<0.05) .Conclusion EA up-regulates HO-1 expression through activating AP-1 during endotoxic shock-induced ALI in rabbits ,thus protecting the lung .

Objective To evaluate the role of activator protein-1 (AP-1) in the up-regulation of heme oxygenase-1 (HO-1) expression during lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.Methods Forty-eight healthy male Sprague-Dawley rats,weighing 200-220 g,aged 2.5-3.0 months,were randomly divided into 4 groups (n=12 each): normal control group (group C),ALI group,curcumin + ALI group (group Cur+ ALI),and curcumin group (group Cur).In groups C and ALI,normal saline 0.5 ml and LPS 10 mg/kg (0.5 ml) were injected intravenously,respectively,30 min after 0.1％ dimethyl sulfoxide (the vehicle for curcumin) 0.5 ml was injected intraperitoneally.In groups Cur+ ALl and Cur,curcumin 20 mg/kg (0.5 ml) was injected intraperitoneally,and 30 min later LPS 10 mg/kg and normal saline 0.5 ml were injected,respectively.The rats were then sacrificed at 6 h after injection of LPS.The lungs were removed for microscopic examination.The pathological changes of the lung were scored.The malondialdehyde (MDA) content,superoxide dismutase (SOD)activity and expression of HO-1,AP-1 and HO-1 mRNA in lung tissues were determined.Results Compared with group C,the pathological score and MDA content were significantly increased,the SOD activity was significantly decreased,and the expression of HO-1,AP-1 and HO-1 mRNA was up-regulated in groups ALl and Cur +AL(l) (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group Cur (P ＞ 0.05).The pathological score and MDA content were significantly higher,and the SOD activity and expression of HO-1,AP-1 and HO-1 mRNA were significantly lower in group Cur + ALl than in group ALI(P ＜ 0.05).Conclusion Transcription factor AP-1 activation is involved in the up-regulation of HO-1 expression during LPS-induced ALI in rats.

Objective To evaluate the effect of electro-acupuncture (EA) at Zusanli and Feishu on endotoxin shock-induced acute lung injury in rabbits.Methods Sixty healthy male New Zealand white rabbits aged 2 months weighing 1.5-2.0 kg were randomly divided into 6 groups (n =10 each):group sham operation (group S); group zinc protoporphyrin-Ⅸ (ZnPP-Ⅸ) (group Z); group lipopolysaccharide (LPS) (group L); group LPS + EA (group EL) ; group LPS + sham EA (group SEL) and group LPS + EA + ZnPP-Ⅸ (group ELZ).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 400 mg/kg and tracheostomized.The animals kept spontaneous breathing.Right internal carotid artery was cannulated for BP monitoring.Ear vein was cannulated for drug administration.LPS 5 mg/kg was injected iv in groups L,EL,SEL,ELZ.Endotoxin shock was confirmed by decrease in BP by 20 ％ of the baseline value and PaO2/FiO2 ≤ 300.ZnPP-Ⅸ (heme oxygenase (HO-1 ) inhibitor)10μmol/kg was injected intraperitoneal at 2 h after LPS injection in groups Z and ELZ.Bilateral 15 min EA stimulation of Zusanli and Feishu ( according to atlas of animal acu-points) was performed once a day for 5 days before LPS administration in groups EL and ELZ.The animals were sacrificed by blood-letting at 6 h after LPS administration.The lungs were removed for microscopic examination (0 =no injury,4 =most severe injury),detection of alveolar epithelial cell apoptosis (by TUNEL) and determination of HO-1 protein and mRNA expression.Results LPS significantly increased lung injury scores,alveolar epithelial cell apoptosis index (the number of apoptotic cells/total cells) and HO-1 protein and mRNA expression.EA significantly attenuated lung injury and alveolar epithelial cell apoptosis induced by LPS and further increased the expression of HO-1 protein and mRNA in group EL as compared with group L.The protective effects of EA was counteracted by ZnPP- Ⅸ in group ELZ.Conclusion EA at Zusanli and Feishu can attenuate endotoxin shock-induced lung injury by up-regulation of HO-1 expression and inhibiting alveolar epithelial cell apoptosis in the lung.

ObjectiveTo evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 (HO-1) expression in the lung tissue in rats with acute lung injury (AL1) induced by endotoxic shock.MethodsForty-eight male SD rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 4 groups ( n =12 each):control group ( group C ) ; endotoxic shock group ( group LS );endotoxic shock +SB203580 (a specific p38MAPK inhibitor) group (group LSS) and SB203580 group (group SB).Normal saline 0.5ml was injected via the femoral vein in groups C and SB,while LPS 10 mg/kg (in 0.5 ml normal saline) was injected via the femoral vein in groups LS and LSS.When MAP was decreased to 75％ of baseline value,10％ dimethyl sulfoxide (DMSO) 0.1 ml was infused via the femoral vein in groups C and LS,while SB203580 5 mol/kg (in 10％ DMSO 0.1 ml) was infused via the femoral vein at a rate of 0.01 ml/min in groups LSS and SB.Arterial blood samples were obtained at 6 h after LPS or normal saline was given for blood gas analysis and oxygenation index (PaO2/FiO2) was calculated.Then the rats were sacrificed and the lungs were removed for microscopic examination.The pathological changes of the lung were scored.The lung water content was calculated.The MDA content,SOD activity,and expression of HO-1 mRNA and protein,p38MAPK protein and phospharylated p38MAPK (p-p38MAPK) protein were determined.ResultsCompared with group C,the oxygenation index and SOD activity were significantly decreased,the pathological score,lung water content and MDA content were significantly increased,and the expression of HO-1 mRNA and protein and p-p38MAPK protein was significantly up-regulated ( P＜0.05),while no significant change was found in p38MAPK protein expression in groups LS and LSS,and no significant change was found in the indexes mentioned above in group SB (P＞0.05).Compared with group LS,the oxygenation index and SOD activity were significantly increased,the pathological score,lung water content and MDA content were significantly decreased,the expression of HO-1 mRNA and protein was significantly up-regulated,and p-p38MAPK protein expression was down-regulated ( P＜0.05),and no significant change was found in p38MAPK protein expression in group LSS ( P＞0.05).ConclusionThe inhibition of p38MAPK signaling pathway can lead to the up-regulation of HO-1 expression in lung tissues in rats with ALI induced by endotoxic shock.

Objective To evaluate the effect of sevoflurane pretreatment on the inflammatory response during renal ischemia-reperfusion (I/R) in rats.Methods Thirty pathogen-free male Sprague-Dawley rats,aged 12-14 weeks,weighing 220-260 g,were randomized into 3 groups (n =10 each) using a random number table:sham operation group (group S),I/R group and sevoflurane pretreatment group (group SP).Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SP groups.In group S inhalation of 3％ sevoflurane in O2 was started at 30 min before I/R and maintained throughout the experiment.Venous blood samples were taken at 3 h of reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were then sacrificed and the left kidneys were removed for microscopic examination and for measurement of the content of tumor necrosis factor-apha (TNF-α),interleukin-6 (IL-6) and intercellular cell adhesion molecule-1 (ICAM-1) in renal tissues (by ELISA).Results Compared with group S,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules (0 =normal,4 =necrosis of whole segment of proximal convoluted tubules),and contents of TNF-α,IL-6 and ICAM-1 were significantly increased in I/R and SP groups (P ＜ 0.05).Compared with group I/R,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules,and contents of TNF-α,IL-6 and ICAM-1 were significantly decreased in SP group (P ＜ 0.05).Conclusion Sevoflurane pretreatment can protect kidney against I/R injury by inhibiting the inflammatory responses in the renal tissues of rats.