OBJECTIVE:To observe the effects of dexmedetomidine on hemodynamics of patients underwent cardiac valve re-placement in the anesthesia induction. METHODS:92 patients underwent cardiac valve replacement were randomly divided into ob-servation group and control group,with 46 patients in each group. Both groups received routine anesthesia induction regimen of midazolam 1-2 mg/kg+ fentanyl 0.05 mg/kg+ propofol 1-2 mg/kg+ cis-atracurium 0.15 mg/kg. Observation group was additionally given dexmedetomidine 0.5 μg/kg,within 10 min with pumps,and then maintained with 0.4 μg/(kg·h)till the end of operation;control group was additionally given constant volume of normal saline with pumps. SBP,DBP,MAP,HR,cardiac output(CO), cardiac index(CI),stroke volume(SV),stroke volume variation(SVV)before anesthesia induction(T0),5 min after medication (T1),2 min after anesthesia induction (T2),1 min after intubation (T3),3 min after intubation (T4) and 5 min after intubation (T5)were recorded in 2 groups as well as OAA/S at T0 and 5 min after pumping dexmedetomidine(T1). ADR of 2 groups during anesthesia was also recorded. RESULTS:There was no significantly difference in SVV of 2 groups at T0-T5 (P>0.05);SBP, DBP,MAP,HR,CO,CI and SV of observation group at T0-T5 were all better than those of control group,with statistical signifi-cance(P<0.01);there was no statistically significant difference in OAA/S of 2 groups at T0(P>0.05),and OAA/S of observa-tion group at T1 was decreased significantly and lower than control group,with statistical significance(P<0.01). There was no sta-tistically significant difference in the incidence of ADR as cardiac arrhythmia and hypotension between 2 groups(P>0.05). CON-CLUSIONS:Dexmedetomidine can reduce the influence of anesthesia on the hemodynamics of patients underwent cardiac valve re-placement with good safety.

Objective To observe the influence of dezocine used before end of operation on postoperative recovery and its inter-vention effect on postoperative pain in the patients with gynecological laparoscopic operation .Methods 60 patients(ASA Ⅰ - Ⅱ ) scheduled hysterectomy operation by gynecological laparoscopy were randomly divided into the observation group (dezocine group , n=30) and the control group(normal saline group ,n=30) .Remifentanil combined with propofol was intravenously given for con-ducting endotracheal intubation general anesthesia .The observation group was given dezocine 0 .1mg/kg(diluting to 10mL by nor-mal saline) at 30-40 min before the end of operation ,while the control group was given the same volume of physiological saline . Blood pressure ,heart rate(HR) ,recovery time ,adverse reactions during the recover period and postoperative pain before induction , after injection and before recovery were recorded .Results The elevation of mean arterial pressure(MAP) and the increase of HR during the recovery period in the observation group were lower than those in the control group (P<0 .05);the recovery time of au-tonomous respiration and extubation time had no statistical difference between the two groups (P>0 .05) .PO2 ,PCO2 and SaO2 had no statistical difference between the two groups (P>0 .05);the postoperative agitation-sedation scores(PASS) and the visual ana-logue scale(VAS) scores in the observation group were significantly lower than those in the control group (P<0 .05) ,and the oc-currence rate of chills also was lower than that in the control group (P<0 .05) .Conclusion Intravenous dezocine before the end of operation in the gynecological laparoscopic operation can effectively inhibit the cardiovascular stress reaction ,does not affect the re-covery speed ,moreover can decrease the restlessness during the recovery period and postoperative pain .

Objective To investigate the effect of bumetanide pretreatment on focal cerebral ischemiareperfusion(I/R) injury in rats.Methods One hundred and five male SD rats weighing 250-300 g were randomly divided into 3 groups (n =35 each ):sham operation group(group S),focal cerebral I/R group (group I/R) and bumetanide pretreatment group (group B).Focal cerebral I/R was induced by occluding the fight middle cerebral artery with a nylon thread with a rounded tip which was inserted into internal carotid artery and advanced cranically until resistance was met in groups I/R and B.In group B bumetanide 30 mg/kg was injected iv at 10 min before ischemia.Neurologic function was assessed and scored-neurologic deficit scores (0 =no deficit,4 =unable to move).The animals were sacrificed at 3,24 and 48 h of reperfusion and their brains were immediately removed for determination of cerebral water content and expression of Na+ -K+ -2Cl- cotransporter 1 (NKCC1).The infarct size was measured at 24 h of reperfusion.Results Focal cerebral I/R significantly increased neurelogic deficit scores,NKCC1 expression,cerebral water content and infarct size in group I/R as compared with group S.Bumetanide pretreatment significantly attenuated cerebral focal I/R-induced increase in neurologic deficit scores,NKCC1 expression and cerebral water content in group B as compared with group I/R.There was no significant difference in infarct size between groups I/R and B.Conclusion Bumetanide pretreatment can reduce focal cerebral I/R injury in rats,and down-regulation of NKCC1 expression is involved in the mechanism.

Objective To evaluate the effect of intrathecal dexmedetomidine on the expression of G-protein-coupled inwardly rectifying K+ channel 1 (GIRK1) in dorsal root ganglia of rats with diabetic neuropathic pain (DNP).Methods A total of 144 healthy adult male SPF Sprague-Dawley rats,aged 8-10 weeks,weighing 200-220 g,were randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),dexmedetomidine group (group D),group DNP,and DNP + dexmedetomidine group (group DD).DNP model was established by single intraperitoneal injection of streptozotocin (STZ) 60 mg/kg.In D and DD groups,dexmedetomidine 1.5 μg/kg was injected intrathecally at 14 days after citrate buffer or STZ injection,while the equal volume of normal saline was given in group C.The mechanical pain threshold was measured before STZ injection (T0),at 14 days after STZ injection (T1),and at 2,4 and 6 h after intrathecal injection (T:2-4).After measurement of the mechanical pain threshold at T2-4,the rats were sacrificed,and the dorsal root ganglia of the lumbar segment (L4-6) were removed for determination of the number of GIRK1 positive cells and expression of GIRK1 protein by immunofluorescence and Western blot,respectively.Results Compared with group DNP,the mechanical pain threshold was significantly increased,the number of GIRK1 positive cells in dorsal root ganglia was significantly increased,and the expression of GIRK1 was significantly up-regulated at T2-4 in group DD (P＜0.05).Compared with group D,the number of GIRK1 positive cells in dorsal root ganglia was significantly increased,and the expression of GIRK1 was significantly up-regulated at T2-4 in group DD (P＜0.05).Compared with group C,the mechanical pain threshold was significantly decreased at T1-4 in group DNP (P＜0.05).Conclusion Intrathecal dexmedetomidine attenuates DNP through up-regulating the expression of GIRK1 in dorsal root ganglia of rats.

Objective To evaluate the role of mammalian target of rapamycin (mTOR) signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats and the relationship with hypoxia-inducible factor 1 (HIF-1α).Methods Seventy-two male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were randomly divided into 4 groups (n=18 each) using a random number table: sham operation group (group S), group I/R, dexmedetomidine group (group Dex) ,and rapamicyn + dexmedetomidine group (group Rpm+Dex).Renal I/R was produced by occlusion of bilateral renal pedicles for 35 min follow by reperfusion in anesthetized rats in I/R, Dex and Rpm+Dex groups.Bilateral renal pedicles were only exposed, and then the abdominal cavity was closed in group S.Dexdetomidine 50 μg/kg was injected intraperitoneally at 30 min before I/R in group Dex.In group Rpm+Dex, rapamicyn 1.5 mg/kg and dexdetomidine 50 μg/kg were injected intraperitoneally, and renal I/R model was established 30 min later.Immediately after onset of reperfusion, and at 4 and 24 h of reperfusion (T1-3) , blood samples were collected from the caudal vein for measurement of serum creatinine and blood urea nitrogen (BUN) concentrations.After blood sampling at T1-3, the rats were sacrificed, and the renal specimens were obtained for detection of HIF-1αt, erythropoietin (EPO) and mTOR expression by Western blot.Their kidneys were removed at T3, and cut into sections which were stained with haematoxylin and eosin and examined under microscope.Acute renal tubular necrosis was scored.The cell apoptosis in renal tissues was detected by TUNEL assay, and apoptosis index (AI) was calculated.Results Compared with group S,the concentrations of serum creatinine and BUN, expression of HIF-1α, EPO and mTOR at T2,3 , AI at T3 and acute renal tubular necrosis score were significantly increased in the other three groups (P＜ 0.05).Compared with group I/R, the concentrations of serum creatinine and BUN were significantly decreased, and the expression of HIF-1α, EPO and mTOR was up-regulated at T2,3 , and AI and acute renal tubular necrosis score were decreased in group Dex (P＜0.05) , and no significant change was found in the parameters mentioned above in group Rpm + Dex (P ＞ 0.05).Conclusion The mTOR signaling pathway is involved in dexmedetomidine-induced reduction of renal I/R injury, which may be related to dexmedetomidine-produced up-regulation of HIF-1α expression in renal tissues of rats.

Objective To investigate the protection effect of dexmedetomidine against H2O2 injury in Human renal tubular epithelial cells(HK-2 cells). Methods HK-2 cells cultured in vitro were randomly divided into four groups(n = 24): control group, dexmedetomidine pretreatment group, H2O2 injury group, H2O2 injury +dexmedetomidine pretreatment group. Cell viabilities were measured by MTS assay, cell apoptosis were detected using flow cytometry, and expression of HIF-1α protein was quantified by western blot. HK-2 cells were divided into 8 groups by combining with three treatment factors such as PI3K inhibitor LY294002, dexmedetomidine and H2O2 injury. MTS assay was used to detect cell viability and western blot was used to quantify protein expression of HIF-1α,Bcl-2 and Bax after treatment in each group. Results Dexmedetomidine significantly increased the level of HIF-1α、 Bcl-2 in HK-2 cells after H2O2 injury, thus improved viabilities and reduced apotosis of cells. Moreover, effect on H2O2 injury cells of Dexmedetomidine was reversed by PI3K inhibitor LY294002. Conclusion Dexmedetomidine could protect against H2O2 injury by up-regulating HIF-1α expression through activating PI3K/Akt/mTOR signaling pathway in HK-2 cells.

BACKGROUND: Nuclear factor-kappa B (NF-κB), as a promoter of inflammatory reaction, stimulates injured parts or transcription of local inflammatory gene, promotes generation of inflammatory factors, and induces pain onset; however, the mechanism on chronic inflammatory pained spinal cord has been less reported.OBJECTIVE: To explore the NF-κB expression in spinal dorsal horn and behavioral hyperalgesia by preparing rat models of complete Freurd's adjuvant arthritis.METHODS: A total of 24 SD rats were randomly divides into sham-surgery group and complete Freund's adjuvant group, with 12 rats in each group. Adjuvant arthritis model was produced by injection of 50 pL complete Fraund's adjuvant (CFA) to the right ankle joint after anesthesia. The same volume saline was injected to the rat right ankle joint in sham-surgery group. The mechanical pain threshold, paw withdrawal thermal latency (PWTL), the diameter of ankle, and NF-kB expression in spinal dorsal horn were investigated 2 days before and 4, 7, 14, 21, and 28 days after CFA injection.thermal symptoms were not obvious. The inflamed symptoms significantly appeared on right ankle joint and developed to food to before injection and sham-surgery group, the mechanical pain threshold was significantly decreased at 4 days after CFA injection, and reached the lowest value at 21 days (P ＜ 0.01). The PWTL was significantly decreased at 4 days after CFA injection significantly increased in Ⅰ-Ⅵ in spinal dorsal horn in the complete Fraund's adjuvant group, which was higher than sham-surgery group (P ＜ 0.01). The results indicated that we could gain stable monoarthritis model by injecting CFA with oil-contained water intorat ankle joint space, and the model shown prolong and significant hyperalgesia to radial thermal and mechanical pressure;meanwhile, the NF-kB expression increased significantly in lamber Ⅰ-Ⅵ in spinal dorsal horn after the ankle joint arthritis.

Objective To evaluate the efficacy of intravenous methylprednisolone for prevention of tracheal intubation-related laryngopharyngeal complications.Methods Three hundred ASA Ⅰ or Ⅱ patients,aged 20-50 yr,weighing 50-80 kg,undergoing elective surgeries,requiring tracheal intubation under general anesthesia,were included and randomized into 5 groups (n =60 each).Methylprednisolone 40 and 80 mg were injected intravenously at 30 min before induction of anesthesia in groups Ⅰ and Ⅱ,respectively,while the equal volume of normal saline was given instead in group Ⅲ.Methylprednisolone 40 and 80 mg were injected intravenously at 30 min before extubation in groups Ⅳ and Ⅴ,respectively.The sore throat,hoarseness and cough were recorded within 24 h after extubation and the severity was evaluated at 1 and 24 h after extubation.Results There was no significant difference in the incidence and severity of sore throat,hoarseness and cough between the five groups (P ＞ 0.05).Conclusion Intravenous methylprednisolone can not effectively prevent tracheal intubation-related laryngopharyngeal complications in patients.

Objective To evaluate the effect of ulinastatin on the expression of aquaporin-4 (AQP4) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods One hundred and thirty-five male adult SpragueDawley rats,weighing 230-280 g,were randomly divided into 3 groups (n =45 each):sham operation group (S group),I/R group and ulinastatin group (group U).The rats were anesthetized with intraperitoneal 10％ chloral hydrate 3.5 ml/kg.Focal cerebral ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 repeffusion.In U group,ulinastatin 100000 U/kg was injected immediately after beginning of reperfusion,while the equal volume of normal saline was injected in S and I/R groups.The rats were sacrificed at 6,24 and 48 h of repeffusion and brains were removed for determination of infract volume (by TTC),brain water content and expression of AQP4 (by immunohistochemistry) in brain tissues.Results Compared with S group,the infarct volume and brain water content were significantly increased,and the expression of AQP4 was up-regulated at each time point in I/R and U groups (P ＜ 0.05).Compared with I/R group,the infarct volume and brain water content were significantly decreased,and the expression of AQP4 was down-regulated at each time point in U group (P ＜0.05).Conclusion The mechanism by which ulinastatin mitigates focal cerebral I/R injury is related to down-regulation of AQP4 expression in brain tissues.

Background and purpose:It has been reported that gap junctional (GJ) function was signiifcantly decreased in hepatocellular carcinoma (HCC) tissues and cell lines. However, the increased GJ suppress tumorigenesis and the development of liver cancer. This study therefore aimed to examine the effect of simvastatin on GJ function between Hep3b cells. Thus, the exploition of drugs to increase GJ function between liver cancer cells will provide an efifcient approach to ifght against liver tumor as well as increase cytotoxicity of antitumor agents.Methods:SRB was used to assay the toxicity of simvastatin. The effect of simvastatin on GJ function was determined by “Parachute” dye-coupling assay and scrape loading/dye transfer assay.Results:Pretreated Hep3b cells with simvastatin at the concentration of 1, 5 or 10 μmol/L for 24 h did not induce the cytotoxicity. So simvastatin at the concentration of 5 and 10 μmol/L would not reduce the amount of GJ on cell membranes. “Parachute” dye-coupling assay showed that the treatment with 5 and 10 μmol/L simvastatin for 4 h enhanced the dye spread through GJ in Hep3b cells. Similarly, scrape loading/dye transfer assay showed that simvastatin could induce the increasing spread of lucifer yellow (Ly, Sigma) around the scoifng cells with increasing concentrations.Conclusion:Simvastatin could increase the GJ function of Hep3b cells.