吸烟患者细胞色素P450酶2E1的表达与七氟醚阻断肾上腺素能反应最低肺泡气浓度的相关性研究

目的 通过检测吸烟患者细胞色素P450酶2E1(cytochrome P450 family 2 subfamily E member 1,CYP2E1)含量变化,分析其与七氟醚阻断肾上腺素能反应的最低肺泡气浓度(minimum alveolar concentration to block the adrenergic response,MACBAR)值的相关性,探讨吸烟对七氟醚MACBAR值的影响及机制.方法 选择ASA分级Ⅰ、Ⅱ级,年龄30~50岁,择期拟在全身麻醉下行腹腔镜胆囊切除术的患者90例.通过询问患者本人及其家属评估两组患者吸烟情况,同时结合血清可替宁含量,将其分为吸烟组(A组,49例)和非吸烟组(B组,41例).采用快诱导气管内插管静吸复合麻醉,两组患者七氟醚目标呼气末浓度平衡时间>20 min,使用气腹刺激,观察MAP和HR变化,采用单次刺激法测定七氟醚MACBAR.手术前1 d抽取患者晨起静脉血5 ml,离心收集血清,检测可替宁和CYP2E1含量.结果 A组、B组诱导前HR和MAP组间比较,差异无统计学意义(P>0.05);组内HR和MAP基础值(气腹针穿刺前3 min、1 min的平均值)比诱导前明显下降(P<0.05);气腹后HR和MAP明显上升,其中MAP在A组升高幅度大于B组(P<0.05),HR组间比较差异无统计学意义(P>0.05).A组七氟醚MACBAR、CYP2E1和可替宁水平均高于B组(P<0.05).A组CYP2E1含量与MACBAR有相关性,且呈正相关(r=0.51,P<0.05).结论 吸烟患者CYP2E1含量与七氟醚MACBAR值有一定相关性,提示吸烟者血清中CYP2E1可能对七氟醚MACBAR值有影响.     

七氟醚预处理可通过抑制星形胶质细胞的活化减少创伤后应激障碍模型大鼠的木僵行为

目的通过观察七氟醚预处理对条件性恐惧模型大鼠木僵行为的影响,探讨星形胶质细胞在大鼠创伤后应激障碍(PTSD)形成过程中的作用及可能的分子机制。方法雄性SD大鼠120只,随机均分为六组:单纯15次电击组(A组)、生理盐水对照组(B组)、0.8%七氟醚吸入组(C组)、0.8%七氟醚吸入+D-丝氨酸组(D组)、D-丝氨酸组(E组)和D-氨基酸氧化酶(DAAO)组(F组)。除A组外其余五组大鼠行双侧杏仁核置管,第1天大鼠在A笼接受15次电击处理,第22天在与A笼环境完全不同的B笼,适应192s,记录大鼠基础木僵值,然后给予1次电击刺激。第23天将大鼠放入B笼,记录木僵率,比较两次木僵率,确定大鼠是否出现应激增强的恐惧学习(SEFL)。每组分别在电击后第7、14、21天各处死4只大鼠,留取海马组织,分别采用免疫印迹法和免疫组织荧光法分析星形胶质细胞表面标志物胶质纤维酸性蛋白(GFAP)的表达水平。结果第22天六组大鼠的基础木僵率差异无统计学意义;与第22天比较,第23天除C组外,其余五组木僵率明显升高(P0.05);与A组比较,C、D、F组木僵率均明显下降(P0.05),E组木僵率明显升高(P0.05)。与第7天比较,第21天A、B、D、E和F组海马组织中的GFAP的表达明显增加(P0.05);与A组比较,C、D、F组海马GFAP的表达明显减少(P0.05),E组海马GFAP的表达明显增加(P0.05)。结论 0.8%七氟醚预处理能减轻PTSD模型大鼠的木僵行为,这可能部分与其抑制星形胶质细胞的活化,从而减少D-丝氨酸的释放有关。     

吸入不同浓度异氟醚对大鼠肺脏磷脂合成的影响

目的探讨吸入不同浓度异氟醚(Iso)对正常大鼠肺脏磷脂酰胆碱(PC)合成代谢的影响。方法78只Wistar大鼠随机取出6只设为空白组(E组),吸入空气。剩余大鼠随机均分为四组,每组又分为吸入4、8h和吸入8h停药2h亚组,每亚组6只。采用高效液相色谱法(HPLC法)测定支气管肺泡灌洗液(BALF)中PC浓度,RT-PCR和蛋白质免疫印迹法(WesternBlot)分别检测肺组织磷酸胆碱二胞苷酰基转移酶(CCT)基因及其蛋白的表达。结果各组间肺组织CCTmRNA和匀浆中CCT蛋白的表达差异无统计学意义。B2组、C2组BALF中PC含量及肺组织微粒体CCT蛋白的表达量均低于E组和B1组、C1组(P<0.05),停药后2h恢复。吸入Iso8h时,B2组、C2组BALF中PC含量及肺组织微粒体CCT蛋白的表达量均低于D2组(P<0.05),同时C2组低于A2组(P<0.05)。结论长时间吸入较高浓度的异氟醚可降低大鼠正常肺脏磷脂合成水平,其机制可能与CCT活性降低有关。     

不同浓度七氟醚对大鼠原代皮质神经元的影响

目的评价不同浓度七氟醚对大鼠原代皮质神经元的毒性作用。方法出生24h内的SD大鼠48只,体外培养大鼠皮质神经元并接种于6孔板(2cm)或12孔板(4.5 mm)培养皿,采用随机数字表法分为四组:1%七氟醚处理组(A组)、2%七氟醚处理组(B组)、4%七氟醚处理组(C组)和对照组(D组),每组12只。A、B、C组神经元分别给予1%、2%和4%浓度的七氟醚处理6h,D组神经元正常培养,采用CCK-8法测定细胞存活率,采用乳酸脱氢酶(LDH)法测定细胞死亡率,采用免疫蛋白印迹(Western blot)法测定凋亡蛋白caspase-3 17kDa片段评价细胞凋亡和促凋亡蛋白Bid、Bim和Puma的表达。结果 B、C组神经元的存活率明显低于D组,死亡率明显高于D组,caspase-3的17kDa片段、Bid、Bim和Puma表达明显高于D组(P0.05);C组神经元的存活率明显低于B组,死亡率明显高于B组,caspase-3的17kDa片段、Bid、Bim和Puma表达明显高于B组(P0.05)。A、D组各指标差异均无统计学意义。结论随着吸入七氟醚浓度的升高,七氟醚可能通过促进促凋亡蛋白Bid、Bim和Puma的表达增加对神经元的毒性作用。     

七氟醚静-吸复合麻醉对原位肝移植手术患者围术期细胞因子的影响

目的观察七氟醚静-吸复合麻醉对原位肝移植手术患者围术期核因子-κB(NF-κB)及肿瘤坏死因子α(TNF-α)和白细胞介素-8(IL-8)的影响。方法 90例行经典非转流式原位肝移植手术的终末期肝病患者,随机均分为异氟醚组(I组)和七氟醚组(S组),两组均采用静-吸复合麻醉,静脉麻醉药为丙泊酚。分别于术前(T1)、无肝期前(T2)、无肝期35min(T3)、新肝期30min(T4)、新肝期2h(T5)及术后12h(T6),静脉采血检测TNF-α及IL-8。新肝再灌注后2h取部分移植肝组织,用于测定肝组织中NF-κB蛋白表达量及其入核后与靶基因的结合活性。结果与T1时比较,T3~T5时两组患者TNF-α、IL-8水平明显升高(P0.05或P0.01)。T3~T5时S组患者TNF-α、IL-8水平均明显低于I组(P0.05或P0.01);S组患者再灌注后肝组织中NF-κB蛋白表达量明显低于I组(P0.05)。结论与异氟醚比较,肝移植手术中应用七氟醚静-吸复合麻醉可以降低NF-κB、TNF-α和IL-8的表达,减轻肝缺血-再灌注损伤,对保护肝组织有利。     

孕早期安氟醚麻醉对大鼠子代海马NR2B表达的影响

目的 评价孕早期安氟醚麻醉对大鼠子代海马N-甲基-D-天冬氨酸受体2B亚基(NR2B)表达的影响.方法 孕8～10 d SD大鼠30只,体重200～250 g,采用随机数字表法,将其随机分为3组(n=10):对照组(C组)、吸入安氟醚4h组(E1组)和吸入安氟醚8h组(E2组).E1组和E2组分别吸入1.7％安氟醚4和8h,氧流量为2 L/min,C组吸入等流量氧气.分别于出生后20和30d,采用Morris水迷宫系统测定子鼠的认知功能.于水迷宫实验结束后第2天,取各组子鼠海马组织,分别采用PCR和免疫组化法测定NR2B mRNA及蛋白的表达.结果 与C组比较,E1组和E2组子鼠出生后20和30 d时逃避潜伏期延长,穿越平台次数减少,平台象限停留时间缩短(P＜0.05),海马NR2B mRNA及蛋白表达下调(P＜0.05);与E1组比较,E2组子鼠出生后20和30 d时海马NR2B mRNA及蛋白表达比较差异无统计学意义(P＞0.05).结论 孕早期安氟醚麻醉可降低大鼠子代的认知功能,其机制与抑制大鼠子代海马NR2B表达有关.     

rhALR在大鼠部分肝移植术后肝再生中的作用及其机制研究

目的 探讨大鼠部分肝移植术后腹腔注射重组人肝再生增强因子(recombinant human augmenter ofliver regeneration,rhALR)促进肝移植术后肝细胞再生的作用及其机制.方法 建立大鼠原位60% 肝脏移植模型,部分肝移植术后腹腔注射rhALR 40 μg/kg 2 次/d(实验组,对照组注射等体积的注射用水);取术后第1、2、3、5、7 天大鼠血清及肝组织,检测血清谷丙转氨酶(ALT),测定肝细胞PCNA LI 的变化,RT-PCR 检测肝组织IL-6 mRNA Cyclin-D1 mRNA 的表达.结果 实验组(A 组)与对照组(B 组)比较,术后第1、2 天A 组血清ALT 显著低于B 组.A 组术后第1、2、3、5 天的PCNA LI 均明显高于B 组同一时点的PCNA LI(P<0.05).A 组术后第2 天的肝细胞AI 明显低于B 组同一时点的肝细胞AI(P<0.05);A 组术后肝组织IL-6 mRNA 的表达与B 组在各观察时点间比较均无统计学差异(P>0.05);A 组术后第1 天肝组织Cyclin D1 mRNA 的表达明显高于B 组同时点的表达(P<0.05),其余观察时点无明显差异.结论 大鼠部分肝移植术后应用rhALR 可以明显促进肝细胞的再生,降低血清ALT,稳定肝细胞膜,保护肝细胞功能.rhALR 促进大鼠部分肝移植术后的肝再生可能并不是通过上调启动阶段重要因子IL-6 mRNA 的表达发挥作用,而是通过上调增殖阶段重要因子CyclinD1mRNA 的表达发挥作用.     

七氟醚预处理对大鼠缺血-再灌注肝脏NF-κB及ICAM-1表达的影响

目的 探讨核因子-κB(NF-κB)和细胞问粘附分子-1(ICAM-1)在七氟醚保护大鼠肝脏缺血-再灌注损伤机制中的作用.方法 将40只SD成年雌性大鼠,随机均分为四组:假手术组(N组),缺血-再灌注组(IR组),七氟醚组(S组),七氟醚缺血-再灌注组(SIR组),每组10只.肝脏缺血1 h、再灌注2 h后取循环血和肝脏,N组、S组作为对照;IR组和SIR组阻断支配大鼠肝脏左叶和中叶的门静脉造成约70%肝脏缺血-再灌注模型,缺血1 h、冉灌注2 h后取材.测定大鼠血清丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)作为肝损害的标志被检测,光镜观察组织学病理改变,电镜下观察肝细胞的超微结构,采用免疫组织化学法检测肝组织NF-κB活性和ICAM-1水平.结果 SIR组肝ALT、AST酶升高受到显著抑制(P＜0.05),电镜显示SIR组细胞拟伤程度小于IR组,SIR组NF-κB和ICAM-1表达低于IR组(P＜0.05).结论 七氟醚能抑制肝缺血-再灌注细胞的NF-κB和ICAM-1表达;NF-κB可能通过调控ICAM-1的表达在缺血-再灌注损伤中发挥作用.     

孕早期七氟醚麻醉对子代大鼠认知功能的影响

目的 评价孕早期七氟醚麻醉对子代大鼠认知功能的影响.方法 孕5～7d的SD大鼠30只,采用随机数字表法,将其随机分为3组(n=10):正常对照组(C组)、吸入七氟醚4h组(S1组)和吸入七氟醚8h组(S2组).S1组和S2组分别吸入95％氧气-1.8％七氟醚4h和8h,氧流量2L/min,C组吸入95％氧气8h.分别于出生后20、30 d取5只母鼠的子鼠,采用Morris水迷宫实验测定认知功能,持续7d,然后处死子代大鼠,分离海马组织,测定N-甲基-D-天冬氨酸受体2B亚基(NR2B)mRNA及其蛋白和hippyragranin mRNA的表达水平.结果 3组子代大鼠水迷宫实验结果、NR2B mRNA及其蛋白和hippyragranin mRNA表达水平差异均无统计学意义(P＞0.05).结论 孕早期七氟醚麻醉对子代大鼠认知功能无影响.     

地氟醚预处理与缺氧/复氧损伤内皮细胞凋亡相关基因表达

目的 观察地氟醚预处理对缺氧/复氧(A/R)损伤内皮细胞凋亡相关基因Bcl-2及Bax表达的影响.探讨地氟醚预处理抑制细胞凋亡的机制.方法 选用人脐静脉内皮细胞株(ECV304).将细胞分为五组,即A/R组(A组)、A/R 肿瘤坏死因子α(TNF-α)10 ng/ml组(B组)、地氟醚1.0MAC预处理 A/R组(C组)、地氟醚1.0 MAC预处理 A/R TNF-α 10 ng/ml组(D组)和空白对照组(E组).应用Real-time PCR、Western Blot方法检测各组细胞中Bcl-2及Bax mRNA和蛋白水平.结果 Real-time PCR和Western Blot结果提示,与E组相比,A、B组Bcl-2表达降低,Bax表达升高(P<0.05或P<0.01).经地氟醚预处理后,C、D组细胞较相应未经预处理的A、B组Bcl-2表达增加.Bax表达降低(P<0.05或P<0.01).结论 地氟醚预处理可通过调节Bcl-2及Bax的表达来抑制缺氧/复氧所引起的内皮细胞凋亡.     

Extrahepatic metabolism of sevoflurane in children undergoing orthotopic liver transplantation

BACKGROUND: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation. METHODS: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode. RESULTS: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 microM (sevoflurane group) versus 1.4 +/- 0.5 microM (isoflurane group) P < 0.05). CONCLUSIONS: These results demonstrate the existence of an extrahepatic metabolism of sevoflurane at least in children with end-stage liver disease.     

Extrahepatic Metabolism of Sevoflurane in Children Undergoing Orthotopic Liver Transplantation

Background: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation.

Methods: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode.

Results: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 [mu]M (sevoflurane group) versus 1.4 +/- 0.5 [mu]M (isoflurane group) P < 0.05).     

七氟醚和异丙酚复合麻醉下活体肝移植术病人围术期心肌损伤的比较

目的 比较七氟醚和异丙酚复合麻醉下活体肝移植术病人围术期心肌损伤的程度,为活体肝移植术选择适宜的麻醉方法.方法 拟行活体肝移植术病人40例,ASAⅡ～Ⅳ级,肝功能Child-Pugh分级B或C级,年龄40～67岁,体重47～95 kg,随机分为2组:七氟醚复合麻醉组(S组)和异丙酚复合麻醉组(P组),每组20例.麻醉诱导:静脉注射咪达唑仑0.1 mg/kg、舒芬太尼1μg/kg和顺苯磺酸阿曲库铵0.15 mg/kg,气管插管后行机械通气.麻醉维持:S组吸入1.6%～3.0%七氟醚,P组靶控输注异丙酚,血浆靶浓度2～4 μg/ml;两组均静脉输注舒芬太尼0.5～1.0μg·kg-1·h-1,间断静脉注射顺苯磺酸阿曲库铵维持肌松.分别于切皮前即刻、无肝期5、30 min、新肝期5、30 min和术毕时,记录HR、MAP、CVP、平均肺动脉压(MPAP)、肺动脉毛细血管楔压(PCWP)、CO和S(v)O2.于切皮前即刻、无肝期30 min、新肝期30 min、术毕、术后24、48和72 h时,采集中心静脉血样,测定血清心肌肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)的浓度.记录术后不良事件的发生情况.结果 两组各时点HR、MAP、CVP、MPAP、PCWP、CO、S(v)O2以及血清cTnI和CK-MB的浓度比较差异无统计学意义(P>0.05);与切皮前即刻比较,新肝期30 min至术后48 h时血清cTnI和CK-MB的浓度升高(P<0.05或0.01).结论 七氟醚和异丙酚复合麻醉时活体肝移植术病人围术期心肌损伤的程度无差别.     

七氟醚不同吸入时间对老年大鼠认知功能的影响

目的 评价七氟醚不同吸入时间对老年大鼠认知功能的影响.方法 健康SD雄性大鼠40只,月龄18月,体重(600±50)g,采用完全随机法分为5组(每组8只):对照组(C组)、吸入3％七氟醚0.5 h组(S1组)、吸入3％七氟醚1h组(S2组)、吸入3％七氟醚2h组(S3组)、吸入3％七氟醚4h组(S4组).所有组于干预结束后第2天行水迷宫实验,于水迷宫实验结束后15 min处死大鼠,取海马组织,采用Western blot法测定海马N-甲基-D-天门冬胺酸受体2B亚基(N-methyl-D-aspartatereceptor type 2B,NR2B)的表达.结果 与C组平台穿越次数[(5.5±1.2)次]比较,S1组[(7.3±1.7)次]明显增多(P＜0.05),S3组[(3.8±1.0)次]和S4组[(1.9±1.0)次]均明显减少(P＜0.05);与S3组比较,S4组减少较为明显(P＜0.05).与C组目标象限停留时间[(48.2±6.2)s]比较,S1组[(56.8±5.1)s]明显延长(P＜0.05),S3组[(39.1±4.0)s]和S4组[(31.6±3.2)s]均明显缩短(P＜0.05);与S3组比较,S4组缩短较为明显(P＜0.05).与C组(1.00)比较,S1组(0.69±0.88)NR2B蛋白相对密度减少(P＜0.05),S3组(1.47±0.17)和S4组(2.17±0.10)NR2B蛋白相对密度均增多(P＜0.05),与S3组比较,S4组增多更为明显(P＜0.05).结论 吸入3％七氟醚2h或4h均可导致老年大鼠认知功能下降,吸入3％七氟醚4h更为明显,其机制可能与海马中过度表达NR2B蛋白有关.     

Renal safety and extrahepatic defluorination of sevoflurane in hepatic transplantations

BACKGROUND: The main metabolic pathway for defluorination of sevoflurane in the liver produces inorganic fluoride (Fl). The metabolism and effect of sevoflurane on the kidney is not clear during anhepatic phase in liver transplantation. The goal of the present study was to investigate the metabolism and renal effect of sevoflurane by measuring plasma and urine inorganic fluoride, urinary N-acetyl-glucosaminidase (NAG), and plasma creatinine levels in patients undergoing liver transplantations. METHODS: After institutional approval and informed consent, we studied nine cases of orthotopic liver transplantation after anesthesia was induced with 5 mg . kg(-1) thiopental, 1 mug . kg(-1) fentanyl intravenously, the trachea was intubated after vecuronium bromide 0.1 mg . kg(-1). Anesthesia was maintained with sevoflurane (2%), O(2), and N(2)O at a total gas flow of 6 L . min(-1) using a semiclosed circle system with a sodalime canister. Blood and urine samples were obtained to measure plasma and urine fluoride concentrations and urinary NAG excretions before induction (P0), hourly during resection (P1, P2, P3), every 15 minutes during anhepatic phase (A1, A2, A3), hourly after reperfusion (neohepatic phase) (N1, N2, N3), and postoperative first hour (Po1). Preoperative (T0) and postoperative day 1 (T1), 3 (T3), 7 (T7) plasma blood urea nitrogen (BUN) and creatinine (Cr) levels were also recorded. RESULTS: Mean duration of surgery was 9:06 +/- 0:09 hours. Mean inorganic fluoride concentrations in plasma were in the range of 0.71 +/- 0.30 to 28.73 +/- 3.31 mumole . L(-1). In P3, N1, N2, N3, increases in plasma inorganic fluoride concentrations were significant (P < .05) and reached a peak value at Po1. The mean urine inorganic fluoride concentrations were 12.49 +/- 2.04 to 256.7 +/- 49.62 mumole . L(-1). In A2, A3, N1, N2, and N3, mean urine inorganic fluoride concentrations were significantly increased (P < .05) and the peak value was observed at Po1. Mean NAG concentrations in urine varied (5.6 +/- 1.6 IU . L(-1) to 12.5 +/- 1.14 IU . L(-1)) and peak level was observed at 30 minutes of the anhepatic phase (A2), which did not exceed the normal values for urine NAG levels (1.5 to 6.1 U . L(-1)). No impairment was observed in serum BUN and creatinine levels at any time. While there was only a slight increase in NAG during anhepatic phase, there was no change in plasma F1. CONCLUSIONS: Sevoflurane seemed to have minimal effect on kidney functions of BUN and Cr levels during liver transplantation. Although urine F1 and NAG levels increased during the anhepatic phase plasma F1, BUN, and Cr levels did not, suggesting that renal F1 production may occur in the absence of hepatic function. The renal effect of sevoflurane in chronic liver disease is controversial and must be investigated in further studies.     

Inhibited hypothalamic histamine metabolism during isoflurane and sevoflurane anesthesia in rats

Background : Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism.
Methods : Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test.
Results : Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation.
Conclusions : Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.     

七氟烷预先给药对大鼠肺缺血再灌注时紧密连接蛋白表达的影响

目的 探讨七氟烷预先给药对大鼠肺缺血再灌注时紧密连接蛋白(Occludie和ZO-1)表达的影响.方法 雄性Wistar大鼠96只,体重250～350 g,随机分为4组(n=24):假手术组(S组)仅游离左肺门,但不阻断;肺缺血再灌注组(I/R组)采用阻断左肺门45 min恢复灌注120 min的方法制备大鼠肺缺血再灌注模型;七氟烷组(Sevo组)吸入2.2%七氟烷30 min后游离肺门,但不阻断;七氟烷预先给药组(SP组)吸入2.2%七氟烷30 min后制备模型.于缺血45 min、再灌注60和120 min(T1～3)时各组随机取6只大鼠处死取肺,称重后计算肺湿干重比,光镜下观察肺组织病理学结果,采用Western blot法检测肺组织Occludin和ZO-1的表达.于再灌注120 min时各组余6只大鼠行支气管肺泡灌洗,取左颈动脉血样,采用Bradford法测定支气管肺泡灌洗液蛋白及血清总蛋白浓度,计算肺血管通透性指数.结果 与S组比较,I/R组和SP组T2,3时肺湿干重比、T3时肺血管通透性指数升高,肺组织Occludin和ZO-1表达下调(P＜0.05),Sevo组上述指标差异无统计学意义(P＞0.05);与I/R组比较,SP组T2,3时肺湿干重比、T3时肺血管通透性指数降低,肺组织Occludin和ZO-1表达上调(P＜0.05).SP组肺组织病理学损伤较I/R组明显减轻.结论 七氟烷预先给药可能通过上调Occludin和ZO-1的表达减轻大鼠肺缺血再灌注损伤.     

反复吸入七氟醚对老龄大鼠海马组织Apaf-1和Caspase-9 mRNA表达的影响

目的 探讨反复吸入七氟醚对老龄大鼠海马组织凋亡蛋白酶活化因子-1(Apaf-1)及半胱氨酸天冬氨酸蛋白酶-9(Caspase-9)mRNA表达的影响.方法 健康Wistar大鼠30只,月龄22月,体重380～770 g,雌雄各半,随机分为4组:对照组(n=8,Ⅰ组)、2%七氟醚组(n=8,Ⅱ组)、3%七氟醚组(n=8,Ⅲ组)及颈总动脉结扎+2%七氟醚组(n=6,IV组).Ⅰ组不吸入七氟醚,Ⅱ组及Ⅲ组分别吸入2%、3%七氟醚,100 min/d,连续5 d.Ⅳ组结扎左侧颈总动脉,1周后吸入2%七氟醚,100 min/d,连续5 d.停止吸入七氟醚后第1天开始采用Morris水迷宫实验测定大鼠认知功能,4次/d,连续测定5 d(T_(1～5)),记录潜伏期、平台象限活动时间与总游泳时间的百分比(Tp/T)及撤去平台后2 min内的游泳轨迹.水迷宫实验结束后采用RT-PCR法测定海马组织Apaf-1、Caspase-9 mRNA的表达水平.结果 与T_1时比较,Ⅰ组T_(3～5)、Ⅱ组及Ⅲ组T_(2～5)时、Ⅳ组T_(4,5)时潜伏期缩短(P<0.05或0.01);与Ⅰ组比较,Ⅲ组T_1时、Ⅳ组T_(1～5),时潜伏期延长,Ⅲ组及Ⅳ组Tp/T降低,Ⅳ组Caspase-9 mRNA表达上调(P<0.05或0.01).撤去平台后,Ⅱ组大鼠游泳轨迹明显集中在平台象限(Ⅳ象限),Ⅲ组和Ⅳ组大鼠游泳轨迹明显散乱.结论 反复吸入七氟醚可导致老龄大鼠认知功能障碍,其机制与海马组织Apaf-1及Caspase-9 mRNA的表达无关.     

七氟醚预处理对大鼠心肌缺血再灌注时Toll 样受体4表达的影响

目的 探讨七氟醚预处理对大鼠心肌缺血再灌注时Toll样受体4(TLR4)表达的影响.方法 清洁级健康雄性SD大鼠30只,体重250～300 g,采用随机数字表法,将大鼠随机分为3组(n=10):假手术组(S组)开胸暴露30 min,左冠状动脉前降支仅穿线不结扎;心肌缺血再灌注组(IR组)采用结扎左冠状动脉前降支30 min,再灌注2 h的方法 制备大鼠心肌缺血再灌注模型;七氟醚预处理组(SP组)吸入2.5%七氟醚30 min,洗脱15 min后制备模型.于再灌注2 h时处死大鼠取心脏,观察心肌组织病理学结果,采用Western blot法检测TLR4、NF-κB和TNF-α的蛋白表达水平.结果 与S组比较,IR组和SP组TLR4、NF-κB和TNF-α的蛋白表达上调(P＜0.05);与IR组比较,SP组TLR4、NF-κB和TNF-α的蛋白表达下调(P＜0.05).病理学结果 显示:SP组心肌细胞损伤较IR组减轻.结论 七氟醚预处理可通过抑制TLR4表达上调降低炎性反应,从而减轻大鼠心肌缺血再灌注损伤.

Abstract：

Objective To investigate the effect of sevoflurane preconditioning on the expression of Toll-like receptor 4(TLR4) during myocardial ischemia reperfusion(IR) in rats.Methods Thirty male SD rats weighing 250-300 g were randomly divided into 3 groups (n=10 each):sham operation group (S group) , IR group and sevoflurane preconditioning group(SP group).Myocardial ischemia was produced by temporary ligation of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion. In SP group, the animals inhaled 2.5% sevoflurane for 30 min followed by 15 min washout before ischemia. The rats were sacrificed at 2 h of reperfusion, hearts removed and myocardial tissues obtained for microscopic examination.The expression of TLR4, NF-κB and TNF-α was detected using Western blot. Results The expression of TLR4, NF-κB and TNF-α was significantly up-regulated in IR and SP groups compared with group S (P＜0.05).The expression of TLR4, NF-κB and TNF-α was significantly down-regulated in group SP compared with group IR (P＜0.05).The myocardial injury was attenuated in group SP.Conclusion Sevoflurane preconditioning can attenuate myocardial IR injury by inhibiting the up-regulation of TLR4 expression and reducing the inflammatory response.