Objective To investigate the effect of creatine phosphate on perioperative myocardial injury caused by living donor liver transplantation(LDLT)in adult patients.Methods Forty ASA Ⅱ -Ⅳ patients(liver function Child-Pugh grade B or C)aged 45-62 yr weighing 47-91 kg undergoing LDLT were randomly divided into 2 groups(n = 20 each): control group(group C)and creatine phosphate group(group CP).In group CP,creatine phosphate 30 mg/kg was injected intravenously at skin incision followed by creatine phosphate infusion at 4 mg· kg- 1 · h- 1 until the end of surgery.In group C,equal volume of normal saline was infused instead of creatine phosphate.HR,MAP,CVP,PCWP,CO and SvO2 were recorded immediately before skin incision,at 5 and 30 min of anhepatic phase,at 5 and 30 min of neohepatic phase and at the end of operation.Blood samples were taken from central vein immediately before skin incision(baseline,T0),at 30 min of anhepatic phase(T1),at 30min of neohepatic phase(T2),at the end of operation(T3)and at 4 and 24 h after operation(T4,5)for determination of serum cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)concentrations and lactate dehydrogenase(LDH)activity.Postoperative adverse events were recorded.Results The serum cTnI and CK-MB concentrations and LDH activity were significantly increased at T2-5 as compared with the baseline value at T0 in both groups(P ＜0.05 or 0.01).MAP and CO were significantly higher from 5 min of neohepatic phase to the end of operation,the serum cTnI and CK-MB concentrations and LDH activity were significantly lower at T2-5,and the incidence of ventricular arrhythmia was significantly lower in group CP than in group C(P ＜ 0.05 or 0.01).Conclusion Creatine phosphate can attenuate perioperative myocardial injury caused by LDLT in adult patients.

Objective To evaluate the effects of different methods of administration on clinical pharmacodynamics of cisatracurium during liver transplantation.Methods Twenty-four ASA physical status Ⅲ patients of both sexes,aged 18-63 yr,weighing 60-88 kg,with body mass index of 20-30 kg/m2,scheduled for elective liver transplantation,were randomly divided into 2 groups (n =12 each):continuous infusion group (group C) and intermittent bolus injection group (group Ⅰ).The total intravenous anesthesia was used during surgery.When T1 recovered to 10％ of control height after induction of anesthesia,continuous infusion of cisatracurium was started with an initial rate of 1.5 μg· kg-1 · min-1,and the infusion rate was manually adjusted to maintain T1 at about 10％ in group C,and intermittent iv boluses of cisatracurium 0.03 mg/kg were given to maintain T1 ≤ 10％ in group Ⅰ.The use of muscle relaxants was stopped immediately after peritoneum closure.The consumption of cisatracurium per minute,time for T1 to recover from 10％ to 25％,recovery index and time for recovery of spontaneous breathing after surgery were recorded.Results Compared with group Ⅰ,the consumption of cisatracurium per minute was significantly reduced and the time for recovery of spontaneous breathing after surgery was shortened (P ＜ 0.05),and no significant changes were found in the time for T1 to recover from 10％ to 25％ and recovery index in group C (P ＞ 0.05).Conclusion Compared with intermittent bolus injection,continuous infusion of cisatracurium during liver transplantation is helpful in improving the clinical potency of the muscle relaxant and in reducing the occurrence of complications during anesthesia recovery period.

Objective To confirm the protective effect of berberine (BBR) on cold ischemia reperfusion (I/R)-induced liver injury and to show whether the hepatic protection conferred by BBR involves the activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (Akt)/mammalian target of rapamycin(mTOR) signal pathway.Method Adult male Sprague-Dawley rats were assigned randomly to four groups:BBR group (BBR was intragastrically administered at a dose of 100 mg·kg-1 · d-1 2 weeks before hepatic cold I/R treatment),dimethyl sulfoxide (DMSO) group (BBR was replaced by DMSO,and others were the same as BBR group),I/R group (BBR was replaced by normal saline,and others were the same as BBR group) and sham group (normal saline was administered 2 weeks before opening and closing abdomen treatment).Then the rats were sacrificed at 3,6,and 24 h after reperfusion.The liver function,oxidative stress level,apoptosis rate,and the expression of PI3K/Akt/mTOR related pathway proteins were assayed.Result As compared with sham group,the I/R-induced liver tissue displayed severe lobular distortion with widespread necrosis,high level of oxidative stress and apoptosis rate.As compared with I/R group,BBR dramatically attenuated the histopathologic damage,restored the liver function and decreased the oxidative stress level.Simultaneously,BBR significantly ameliorated the apoptosis by decreasing the apoptosis rate,increasing the Bcl-2/Bax ratio and inhibiting caspase-3 activity in rats subjected to hepatic I/R.The expression of p-Akt was effectively upregulated with the inhibited expression of p-mTOR.Conclusion Our result provides robust in vivo evidence that BBR can prevent I/R-induced oxidative stress and apoptosis.The mechanisms involved can be attributed to the activation of P]3K/Akt/mTOR signal pathway.

Kidney plays an important role in maintaining the homeostasis as an important excretory and endocrine organ.The occurrence and development of kidney disease is closely associated with glomerular filtration barrier dysfunction and renal interstitial remodeling.Matrix metalloproteinase-9 (MMP-9),a major enzyme in the extracellular matrix (ECM),plays an important role in the process of kidney disease by regulating the ECM components and its interaction with cytokines.The paper reviews the pathophysiology of MMP-9 in glomerular filtration barrier dysfunction and renal fibrosis to provide a theoretical basis for clinical treatment of kidney disease.

Objective To evaluate the effect of dexmedetomidine on myocardial injury in pediatric patients undergoing living-related liver transplantation. Methods Fifty-eight pediatric patients of both sexes,aged 5-20 months,weighing 4.5-15.0kg,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective living-related liver transplantation,were divided into 2 groups(n=29 each)using a random number table:control group(group C)and dexmedetomidine group(group D).In group D,dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg over 10min starting from the time point immediately before skin incision,followed by an infusion of 0.8 μg·kg-1·h-1 until the end of surgery. The equal volume of normal saline was given instead in group C. Immediately before skin incision(baseline,T0),at 10min of anhepatic phase(T1),at 30min of neohepatic phase(T2)and at the end of surgery(T3),blood samples were obtained from the central vein for determination of serum cardiac troponin I(cTnI),lactate dehydrogenase(LDH),alpha-hydroxybutyrate dehydrogenase(α-HBDH),interleukin-6(IL-6)and IL-10 concentrations. The changing rate of serum cTnI concentrations were calculated at T2. The occurrence of myocardial ischemia and ventricular premature beat and requirement for dopamine were recorded during surgery. Results Compared with the baseline at T0,the serum concentrations of cTnI,LDH and α-HBDH were significantly increased at T2,3,and the serum concentrations of IL-6 and IL-10 were increased at T1-3 in both groups(P<0.05).Compared with group C,the serum concentrations of cTnI,LDH,α-HBDH and IL-6 were significantly decreased at T2,3,the serum concentration of IL-10 was increased at T1-3,the changing rate of serum cTnI concentrations was decreased(P<0.05),and no significant change was found in the incidence of myocardial ischemia and ventricular premature beat and requirement for dopamine in group D(P>0.05).Conclusion Dexmedetomidine can attenuate the myocardial injury to some extent in pediatric patients undergoing living-related liver transplantation.

Objective To evaluate the effect of dexmedetomidine pretreatment on activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway during intestinal injury in rats undergoing liver transplantation.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,weighing 220-250 g,aged 8-10 weeks,were divided into 4 groups (n =8 each) using a random number table:sham operation group (S group),liver transplantation group (LT group),dexmedetomidine pretreatment group (D group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (D+A group).The model of liver transplantation was established in LT,D and D+A groups except group S.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally at 30 min before skin incision.In group D+A,atipamzole 250 μg/kg was injected intraperitoneally at 5 min before administration of dexmedetomidine.At 6 h of reperfusion,blood samples were collected from the inferior vena cava for determination of serum concentrations of intestinal fatty acid binding protein (iFABP),lipopolysaccharide (LPS),tumor necrosis factor-alpha (TNF-ct) and high-mobility group box 1 protein (HMGB1).Intestinal specimens were then obtained for examination of the pathological changes of intestinal tissues (under light microscope) and for determination of the expression of activated caspase-3,phosphorylated JAK2 (p-JAK2),phosphorylated STAT1 (p-STAT1) and phosphorylated STAT3 (p-STAT3).Intestinal damage was assessed and scored.Wet/dry weight ratio (W/D ratio) was calculated.Results Compared with group S,the concentrations of iFABP,LPS,TNF-α and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,pSTATI and p-STAT3 in intestinal tissues was up-regulated in LT and D groups (P＜0.05).Compared with group LT,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly decreased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was down-regulated in group D (P＜0.05).Compared with group D,the concentrations of iFABP,LPS,TNF-cα and HMGB1 in serum,intestinal damage scores and W/D ratio were significantly increased,and the expression of activated caspase-3,p-JAK2,p-STAT1 and p-STAT3 in intestinal tissues was up-regulated in group D+A (P＜0.05).The pathological changes of intestinal tissues were significantly attenuated in group D as compared with group LT.Conclusion The mechanism by which dexmedetomidine pretreatment reduces intestinal injury may be related to inhibition of JAK/STAT signaling pathway activation in rats undergoing liver transplantation.

Objective To investigate the effect of berberine pretreatment on hypoxia/reoxygenation (H/R)-induced apoptosis in human renal tubular epithelial cells.Methods The human renal tubular epithelial cells were cultured and seeded in culture dishes (2 ml/dish) or 96-well plates (200 μl/well) with the density of 1 ×106/ml.The cells were then randomly divided into 4 groups (n =30 each):normal control group (group C),berberine group (group B),H/R group and H/R + berberine group (H/R + B group).In groups B and H/R + B,berberine 10 μmol/L was added to the culture medium and the cells were incubated for 2 h.Groups H/R and H/R + B were then exposed to 94％ N2-5％ CO2-1％ O2 for 24 h followed by 3 h reoxygenation.The cell viability,apoptotic rate and level of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected.The expression of caspase-3,activated caspase-3,cytochrome c,glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) was determined.The ratio of Bax/Bcl-2 was calculated.Results Compared with group C,the cell viability,SOD activity and caspase-3 expression were significantly decreased,the apoptotic rate,Bax/Bcl-2 ratio and concentration of MDA were increased,and the expression of activated caspase-3,cytochrome c,GRP78 and CHOP was up-regulated in groups H/R and H/R + B (P ＜ 0.05).Compared with group H/R,the cell viability,SOD activity and caspase-3 expression were significantly increased,the apoptotic rate,Bax/Bcl-2 ratio and concentration of MDA were decreased,and the expression of activated caspase-3,cytochrome c,GRP78 and CHOP was down-regulated in group H/R + B (P ＜ 0.05).Conclusion Berberine pretreatment can inhibit H/R-induced apoptosis in human renal tubular epithelial cells,and inhibition of mitochondrial stress pathway and endoplasmic reticulum stress pathway is involved in the mechanism.

Objective To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) signaling pathway in reduction of acute kidney injury following orthotopic liver transplantation (OLT) by hydrogen-rich saline in rats.Methods Thirty-two healthy adult male SpragueDawley rats,weighing 220-250 g,were randomly assigned into 4 groups (n =8 each) using a random number table:sham operation group (S group),OLT group,hydrogen-rich saline group (HS group),and all-trans retinoic acid (ATRA) group.Laparotomy was performed,and the related blood vessels were isolated in group S.The model of orthotopic autologous liver transplantation was established in OLT,HS and ATRA groups.Normal saline and hydrogen-rich saline 6 ml/kg were injected through the inferior vena cava at 5 min before the portal vein was clamped in OLT and HS groups,respectively.In group ATRA,Nrf2 inhibitor ATRA 7 mg/kg was injected intraperitoneally once a day for 2 consecutive days,the model of orthotopic autologous liver transplantation was established at 16 h after the last injection of ATRA,and the other treatments were similar to those previously described in group HS.At 6 h of reperfusion,blood samples were collected for determination of serum blood urea nitrogen (BUN),creatinine (Cr),interleukin10 (1L-10) and tumor necrosis factor-alpha (TNF-α) concentrations.After blood sampling,the lungs were removed for determination of malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,expression of HO-1,Bcl-2 and Bax mRNA (by using real-time reverse transcriptase polymerase chain reaction),and HO-1 protein expression in lung tissues (by Western blot) and for microscopic examination.The damage to the renal tubules was scored.Results Compared with group S,the serum BUN,Cr and TNF-α concentrations were significantly increased,the serum IL-10 concentrations were decreased,the MDA content and renal tubular damage score were increased,the SOD activity was decreased,and the expression of HO-1 protein and mRNA,and Bcl-2 and Bax mRNA was up-regulated in group OLT (P＜ 0.05).Compared with group OLT,the serum BUN,Cr and TNF-α concentrations were significantly decreased,the serum IL-10 concentrations were increased,the MDA content and renal tubular damage score were decreased,the SOD activity was increased,the expression of HO-1 protein and mRNA and Bcl-2 mR-NA was up-regulated,and the expression of Bax mRNA was down-regulated in group HS (P＜0.05).Compared with group HS,the serum BUN,Cr and TNF-α concentrations were significantly increased,the serum IL-10 concentrations were decreased,the MDA content and renal tubular damage score were increased,the SOD activity was decreased,the expression of HO-1 protein and mRNA and Bcl-2 mRNA was down-regulated,and the expression of Bax mRNA was up-regulated in group ATRA (P＜0.05).Conclusion The mechanism by which hydrogen-rich saline reduces acute kidney injury following OLT is probably associated with activation of Nrf2/HO-1 signaling pathway in rats.

Objective To investigate the effects of ethyl pyruvate (EP) pretreatment on the liver injury in rats undergoing orthotopic liver transplantation (OLT).Methods Forty male adult SD rats,weighing 220-250 g,served as liver transplant donors and recipients.The recipient rats were randomly divided into 3 groups ( n =8 each):sham operation group (group S),OLT group and EP group.Group S only underwent simple laparotomy.The model of OLT was established according to the modified Kamada's two-cuff technique in groups OLT and EP.EP 40 mg/kg was injected via the caudal vein at 1 h before skin incision in group EP.Venous blood samples were taken at 2 h of neohepatic phase to determine the serum activities of alanine amino-transferase (ALT) and aspartate amino-transferase (AST).Hepatic specimens were obtained to detect the content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD).Results Compared with group S,the levels of serum ALT and AST and MDA were significantly increased and the activity of SOD was significantly decreased in groups OLT and EP ( P ＜0.05 or 0.01).The levels of serum ALT and AST and MDA were significantly lower and the activity of SOD was significantly higher in group EP than in group OLT ( P ＜ 0.05 or 0.01 ).Conclusion Ethyl pyruvate pretreatment can attenuate the liver injury in rats undergoing OLT.

Objective To investigate the effects of ulinastatin on the myocardial injury in patients undergoing live donor liver transplantation.Methods Forty patients (AHA classification grade A or B),aged 40-64 yr,with a body mass index of 18-25 kg/m2,scheduled for live donor liver transplantation,were randomly divided into 2 groups ( n =20 each):control group (group C) and ulinastatin group (group U).Anesthesia was induced with midazolam,sufentanil,and cisatracurium besilate.The patients were tracheal intubated and mechanically ventilated.Ulinastatin 300 000 IU in 100 ml of normal saline was infused intravenously over 30 min after anesthesia induction and then the infusion was repeated at 4 h interval until the end of operation in group U,while the equal volume of normal saline was given in group C.Blood samples were taken from the central vein immediately before skin incision (T0,baseline),at 30 min of anhepatic phase (T1),at 30 min of neohepatic phase (T2),and at 0,4 and 24 h after operation (T3-5) for determination of the concentrations of serum cardiac troponin Ⅰ (cTnI),creatine kinase-MB (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP).The changing rates of cTnI and CK-MB at T1-5 were calculated.The use of cardiovascular drugs and cardiovsscular accidents were recorded during operation.Results The serum cTnI,CK-MB and NT-proBNP concentrations were significantly higher at T2-5 than at T0 in the two groups ( P ＜ 0.05).Compared with group C,the serum cTnI,CK- MB and NT-proBNP concentrations at T2-5 were significantly deceased in group U ( P ＜ 0.05).The maximal changing rates of cTnI,CK-MB and NT-proBNP concentrations were 4.71 ± 1.62,6.85 ± 1.53 and 4.96 ± 1.23 respectively in group C,decreased to 3.26 ± 1.51,4.56 ± 1.62 and 3.67 ± 1.02 respectively in group U.There was no significant difference in the incidence of cardiovascular accidents and the use of dopamine between the two groups.Conclusion Intravenous infusion of ulinastatin can attenuate the myocardial injury to some extent in patients undergoing live donor liver transplantation.