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 estimate the maternal.neonatal morbidity associated with induction deliveries compared with spontaneous deliveries in 41 gestational weeks uncomplicated primiparae.Methods Three hundred and seventy.four uncomplicated primiparous deliveries at 41 gestational weeks at Peking Union Medical College Hospital from Sept 2002 to Apr 2007 were reviewed.including 225 women undergoing induced labor and 149 women undergoing spontaneous labor.The induction methods included drug induction (173),rupture of membrane induction(5)and combined drug with rupture of membrane induction(47).The maternal morbidity,delivery method,matemal cost on hospital stay and neonatal asphyxia associated with induction deliveries or spantaneous deliveries were retrospectively analyzed.Results (1)There was no maternal death.The caesarean section rate in the induction group(44.0%,99/225)was significantly higher than that of spontaneous group(18.1%,27/149;P<0.05).(2)No statistically significantdifference(P>0.05)was observed between induction group and spontaneous group in the following puerperal complications:postpartum hemorrhage(2.7%,6/225 and 1. 3%,2/149 respectively),puerperal morbidity(0.9%,2/225 and 0.7%,1/149 respectively),severe amniotie fluid contamination (11.6%,26/225 and 13.4%,20/149 respectively),wound infection(0.9%,2/225 and 0.7%.1/149 respectively),urinary retention(4.4%,10/225 and 3.4%,5/149 respectively),traumata(0.4%,1/225and 0 respectively)and neonatal asphyxia(1.3%,3/225 and 2.0%,3/149 respectively).(3)The average duration of first stage of labor in the induction group(413 min)Was not significantly different from tllat of spontaneous group(461 min;P>0.05).In the induction group,more women had precipitate lahore(P

Objective To evaluate the role of c-AMP-protein kinase A (cAMP-PKA) on 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 180-220 g,aged 2.5-3.0 months,were randomly divided into 4 groups (n =12 each)∶ normal control group (group C),ALI group (group ALI),H89 +ALI group (group H + ALI) and H89 group (group H).In group C,normal saline (solvent for LPS) 0.5 ml was injected via the femoral vein and normal saline (solvent for H89) 0.5 ml was injected subcutaneously 2 h later.In group ALI,10 mg/kg LPS 0.5 ml was injected via the femoral vein and normal saline 0.5 ml was injected subcutaneously 2 h later.In group H +ALI,10 mg/kg LPS 0.5 ml was injected via the femoral vein and 5 mg/kg H89 0.5ml was injected subcutaneously 2 h later.In group H,normal saline 0.5 ml was injected via the femoral vein and 5 mg/kg H89 0.5 ml was injected subcutaneously 2 h later.The rats were then sacrificed at 6 h after iv injection of LPS and the lungs were removed for microscopic examination and lung water content.The pathological changes of the lung were scored.The expression of HO-1 and PKA (by Western blot) and HO-1 mRNA (by RT-PCR) was detected.Results Compared with group C,the pathological score and lung water content were significantly increased,and the expression of HO-1,PKA and HO-1 mRNA was up-regulated in groups ALI and H +ALI (P ＜0.05),and no significant change was found in the parameters mentioned above in group H (P ＞ 0.05).The pathological score and lung water content were significantly higher,and the expression of HO-1,AP-1 and HO-1 mRNA was significantly lower in group H + ALI than in group ALI (P ＜ 0.05).Conclusion Activation of signaling pathway c-AMP-PKA is involved in the up-regulation of HO-1 expression during LPS-induced ALI in rats.

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.

Objective To investigate the effects of CORM-2 via p38 mitogeu-activated protein kinase (p38MAPK) signaling pathway on the expression of the mitochondrial fission protein 1 (Fisl) in lipopolysaccharide (LPS)-induced mouse pulmonary macrophages.Methods The rat subculture alveolar macrophages were seeded on 96 well plates with 2 × 105/ml densities.After 24 hours of culture,it was divided into 4 groups by random number table method:normal control group (group C),group LPS (group L),CO releasing agent CORM-2 + LPS group (group LC),p38MAPK inhibitor SB203580 + CORM-2 + LPS group (group LCS).When the cells were incubated for 24 hours,the mitochondrial MDA content and SOD activity were determined by ELISA kit,the levels of HO-1、mitochondrial fission protein Fis1 and p38 were determined by Western blot,the expressions of HO-1 and mitochondrial fission protein Fis1 were detected by RT-PCR.Results Compared with the C group,the levels of MDA [(2.43 ±0.12) vs.(3.59 ±0.07)],HO-1 [(1.31±0.27) vs.(1.65±0.41)],Fis1 [(1.27±0.23) vs.(1.65±0.41)] andp38 [(1.01 ±0.24) vs.(1.36 ±0.17)] in group L were increased,and the activity of SOD [(81.7 ± 1.62) vs.(54.7 ± 1.62)] was decreased (P ＜ 0.05);Compared with the group L,the MDA content [(3.59 ± 0.07) vs.(3.08 ±0.52)] and the level of Fis1 [(2.01 ±0.35) vs.(1.48 ±0.39)] in group LC were down-regulated,and the levels of SOD [(54.7 ± 1.62) vs.(67.4 ± 1.32)]、and the expressions of HO-1 [(1.65±0.41)vs.(2.25±0.18)] andp38 [(1.36±0.17) vs.(1.78±0.23)] wereup-regulated (P ＜0.05).Compared with the group LC,the MDA content [(3.08 ±0.52) vs.(4.16 ±0.19)] and the expression of Fis1 [(1.48 ±0.39) vs.(1.96 ±0.31)] in group LCS were increased,and the level of SOD [(67.4±1.32)vs.(45.9±1.52)]、and the expressions of HO-1 [(2.25±0.18)vs.(1.78± 0.19)] and p38 [(1.78 ±0.23) vs.(1.12 ±0.29)] were decreased (P ＜0.05).Conclusions HO-1/CO system inhibits the expression of Fis1 in LPS-induced lung macrophages,which may be regulated by p38MAPK signaling pathway.

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 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.

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.