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Objective To evaluate the effects of OPRM1All8G and CYP3A4*18B genetic polymorphism and the interaction on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and thirty-nine patients (native of Henan province),aged 40-64 yr,weighing 40-70 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective radical resection of lung cancer under general anesthesia,were enrolled in this study.The polymorphic sites of the OPRM1All8G and CYP3A4*18B allele were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group (group AA,group *1/*1),heterozygote group (group AG,group * 1/*18B) and mutation homozygote group (group GG,group *18B/*1SB) according to their genotypes.The patients were divided into 7 groups according to the interaction between the two genes:AA plus *1/*1 group (group Ⅰ),AA plus *1/*18B group (group Ⅱ),AG plus *1/*1 group (group Ⅲ),AG plus *1/*18B group (group Ⅳ),GG plus * 1/*1 group (group Ⅴ),GG plus *1/*18B group (group Ⅵ) and *18B/*18B group (group Ⅶ).Patientcontrolled intravenous analgesia with fentanyl was started at the end of surgery to maintain the visual analogue scale ≤ 3 points.The amount of fentanyl used within 24 and 48 h after surgery was recorded,and the occurrence of adverse reactions within 48 h after surgery was observed.Results The amount of fentanyl used within 24 and 48 h after surgery was significantly higher in group GG than in group AA (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly lower in group *18B/*18B than in group *1/*1 (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly higher in Ⅱ and Ⅳ groups than in group Ⅰ,in group Ⅲ than in group Ⅱ,in group Ⅴ than in Ⅰ-Ⅳ groups,and in group Ⅵ than in Ⅱ and Ⅳ groups,and was significantly lower in group Ⅶ than in Ⅰ-Ⅵ groups (P＜ 0.05).There was no significant difference in the incidence of adverse reactions within 48 h after surgery between groups (P＞0.05).Conclusion OPRM1A1l8G and CYP3A4*18B genetic polymorphism and the interaction are the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.
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Objective To evaluate the effects of sevoflurane on neurogenesis in hippocampal den-tate gyrus(DG)of mice with Alzheimer′s disease. Methods Thirty-six SPF male APP∕PS1 mice, aged 8 months, weighing 30-35 g, were divided into 3 groups(n=12 each)using a random number table:Alzheimer′s disease group(group AD), oxygen group(group O2)and sevoflurane group(group Sev). Another 12 wild-type mice served as control group(group C). In group Sev, 30% sevoflurane was in-haled for 2 h once a day for 3 consecutive days. The mixture of air and oxygen was inhaled in group O2. Morris water maze test was performed on 22 to 28 days after the last sevoflurane inhalation. Then the mice were sacrificed and hippocampi were isolated for determination of doublecortin(DCX)positive cell count (by immunohistochemistry)and neuronal nuclei(NeuN)∕5-bromo-2′-deoxyuridine(BrdU)and glial fi-brillary acidic protein(GFAP)∕BrdU positive cell count in hippocampal DG(by immunofluorescence). Results Compared with group C, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in AD, O2and Sev groups(P<005). There was no significant difference in each parameter between group O2and group AD(P>005). Compared with group O2, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, and DCX, NeuN∕BrdU and GFAP∕BrdU positive cell counts were reduced in group Sev(P<005). Conclusion Sevoflurane leads to cognitive decline through depressing neurogenesis in hippocampal DG of mice with Alzheimer′s disease.
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Objective To evaluate the effect of propofol on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the hippocampus of rats undergoing orthotopic liver transplantation.Methods Twenty-four healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 220-250 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group S);orthotopic liver transplantation group (group O);propofol group (group P).After the rats were anesthetized with chloral hydrate,the model of orthotopic liver transplantation was established according to the method described by Nozato et al.in O and P groups.In group P,30 min infusion of propofol was started at a rate of 20 mg · kg-1 · h-1 via the right femoral vein immediately after onset of reperfusion.At 6 h of reperfusion,blood samples were collected from the infrahepatic vena cava,and then the rats were sacrificed.The hippocampi were harvested for determination of malondialdehyde (MDA)and nitric oxide (NO) contents and superoxide dismutase (SOD) activity.The serum levels of S100β protein and neuron-specific enolase (NSE) were determined by enzyme-linked immunosorbent assay.The expression of JAK2,STAT3 and inducible nitric oxide synthase (iNOS) mRNA was detected by quantitative real-time polymerase chain reaction.The pathological changes of hippocampal tissues were examined under the light microscope,and the cell apoptosis was measured using TUNEL.The apoptotic index was calculated.Results Compared with group S,the serum levels of S100β protein and NSE were significantly increased,the contents of MDA and NO were significantly increased,the activity of SOD was significantly decreased,the expression of JAK2,STAT3 and iNOS mRNA was significantly up-regulated,the apoptotic index was significantly increased (P＜0.05),and the pathological changes of hippocampal tissues were significantly aggravated in the other groups.Compared with group O,the serum levels of S100β protein and NSE were significantly decreased,the contents of MDA and NO were significantly decreased,the activity of SOD was significantly increased,the expression of JAK2,STAT3 and iNOS mRNA was significantly downregulated,the apoptotic index was significantly decreased (P＜0.05),and the pathological changes of hippocampal tissues were significantly reduced in P group.Conclusion Propofol reduces injury to the hippocampus through blocking JAK2/STAT3 signaling pathway in the rats undergoing orthotopic liver transplantation.
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Objective To investigate the effect of dexmedetomidine added to ropivacaine administered locally on prevention of tourniquet?related hypertension in the patients undergoing total knee arthroplast. Methods Ninety patients of both sexes, aged 58-74 yr, weighing 60-78 kg, of American Society of Anesthesiologists physical statusⅠ?Ⅲ, scheduled for elective unilateral total knee arthroplast, were randomly divided into 3 groups ( n=30 each) using a random number table: ropivacaine group ( group R) , dexmedetomidine added to ropivacaine administered locally group ( group D + R ) , and dexmedetomidine administered intravenously + ropivacaine group ( group Div+R ) . Femoral nerve block:0.5% ropivacaine 15 ml was injected in group R; the mixture ( 15 ml) of 0. 5% ropivacaine 20 ml plus dexmedetomidine 60 μg was injected in group D+R; 0.5% ropivacaine 15 ml was injected in group Div+R. Lateral femoral cutaneous nerve block: 0.5% ropivacaine 5 ml was injected in group R; the mixture 5 ml was injected in group D+R; 0.5% ropivacaine 5 ml was injected in group Div+R. General anesthesia was induced after the end of nerve block. In group Div+R, dexmedetomidine was infused as a bolus of 0.5 μg∕kg over 10 min starting from anesthesia induction, followed by an infusion of 0.4 μg·kg-1 ·h-1 until 30 min before the end of surgery. A tourniquet was applied and inflated ( 266-304 mmHg) within 90 min. Before induction of anesthesia ( T0 ) , and at 0, 15, 30, 45, 60, 75 and 90 min after the tourniquet was inflated ( T1?7 ) , mean arterial pressure and heart rate were recorded. The occurrence of hypertension, hypotension, tachycardia and bradycardia was recorded when the tourniquet was inflated. Agitation was assessed and scored after removal of the endotracheal tube. The time for recovery of breathing, emergence time, and time for removal of the endotracheal tube were recorded. Results Compared with group R, the mean arterial pressure and heart rate were significantly decreased at T1?7 in D+R and Div+R groups, the incidence of hypertension and tachycardia was decreased, the incidence of bradycardia was increased, and agitation score was decreased in D+R and Div+R groups ( P0.05). There was no significant difference in the time for recovery of breathing, emergence time, and time for removal of the endotracheal tube between the three groups ( P>0.05 ) . Conclusion Dexmedetomidine added to ropivacaine administered locally can exert effect on prevention of tourniquet?related hypertension in the patients undergoing total knee arthroplast, and the effect is similar to that of dexmedetomidine administered intravenously.