孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响

目的 探讨孕期吸入异氟醚对子代大鼠海马神经元突触可塑性的影响.方法 孕14 d的SD大鼠10只,体重220～250 g,采用随机数字表法,将孕鼠随机分为对照组和异氟醚组,每组5只.对照组大鼠每天单纯机械通气2 h,异氟醚组大鼠每天吸入1.3%异氟醚2 h,至大鼠分娩.子代大鼠出生后4周,采用Morris水迷宫实验测定认知功能,测定结束后处死子代大鼠取脑,分离海马,采用透射电镜观察海马CA1区神经元突触的超微结构,计数海马神经元突触数量,测定突触后致密物质厚度.结果 与对照组相比,异氟醚组子代大鼠逃避潜伏期延长,穿越平台次数减少,海马神经元突触数量减少,突触后致密物质厚度降低(P<0.05).结论 孕期吸入异氟醚可通过抑制子代大鼠海马神经元突触的可塑性而降低其认知功能.

Abstract：

Objective To investigate the effect of isoflurane inhalation during gestation period on plasticity of hippo-campal synapses in offspring rats. Methods Ten healthy pregnant SD rats at 14 day gestation were randomly divided into 2 gorups ( n = 5 each): control group (group C) and isoflurane group (group I). The rats in group C were mechanically ventilated with O2 while in group I the rats inhaled 1.3% isoflurane in O2 for 2 h a day until labor. Four weeks after birth 4 offspring rats from each pregnant rats (2 male, 2 female) were tested for learning and memory abilities using Morris water maze. Then the offspring rats were sacrificed and hippocampi isolated. The synaptic structure of hippocampal CA1 area was examined by trans-electron microscopy. Results Morris water maze test showed that the escape latency was significantly shorter and the number of times of spanning flat roof greater in group C than in group I. The structure of hippocampus was intact in group C but incomplete in group I. Meanwhile the thickness of synaptic density was significantly decreased in group I. Conclusion Isoflurane anesthesia of pregnant rats may induce learning and memory disabilities in offspring rats by inhibiting the plasticity of synaptic structure in hippocampus.     

异氟醚和七氟醚对非体外循环冠状动脉旁路移植术患者心肌保护作用的比较

目的 比较异氟醚和七氟醚对非体外循环冠状动脉旁路移植术患者的心肌保护作用.方法 择期行非体外循环冠状动脉旁路移植术患者40例,性别不限,年龄40～55岁,体重55～94 kg,ASA分级Ⅱ或Ⅲ级,NYHA分级Ⅱ或Ⅲ级.采用随机数字表法,将患者随机分为2组(n=20):异氟醚组(Ⅰ组)和七氟醚组(S组).麻醉诱导:静脉注射咪达唑仑0.08 mg/kg、舒芬太尼2μg/kg和维库溴铵0.1 mg/kg,气管插管后行机械通气.麻醉维持:Ⅰ组吸入异氟醚,初始呼气末浓度1.2%;S组吸入七氟醚,初始呼气末浓度1.7%;两组静脉输注舒芬太尼0.04μg·kg-1·min-1和维库溴铵0.8μg·kg-1·min-1.通过调节异氟醚或七氟醚的呼气末浓度,维持BIS值40～50.分别于切皮前即刻、术毕、术后2和4 h时,采集中心静脉血样,测定血浆MB型肌酸激酶同工酶(CK-MB)的活性和心肌肌钙蛋白Ⅰ(cTnI)的浓度.记录术中心血管不良事件的发生情况.结果 与Ⅰ组比较,S组术中室性早搏、心动过速、心动过缓、室颤和S-T段抬高＞0.1 mV的发生率升高,术后血浆CK-MB活性和cTnI浓度升高(P＜0.05).结论 非体外循环冠状动脉旁路移植术患者异氟醚的心肌保护作用优于七氟醚.

Abstract：

Objective To compare the myocardial protective effects of isoflurane versus sevoflurane in patients undergoing off-pump coronary artery bypass grafting (OPCABG). Methods Forty ASA Ⅱ or Ⅲ patients (NYHA Ⅱ or Ⅲ ) of both sexes, aged 40-55 yr, weighing 55-94 kg, scheduled for elective OPCABG, were randomly divided into 2 groups ( n = 20 each): isoflurane group ( group Ⅰ) and sevoflurane group ( group S). Anesthesia was induced with midazolam, sufentanil and vecuronium. Patients were tracheal intubated and mechanically ventilated. Anesthesia was maintained with inhalation of isoflurane or sevoflurane and infusion of sufentanil and vecuronium. In group Ⅰ, the initial end-tidal concentration of isoflurane was 1.2%. In group S, the initial end-tidal concentration of sevoflurane was 1.7 %. BIS value was maintained at 40-50 by adjusting the end-tidal concentration of isoflurane or sevoflurane. The central venous blood samples were collected immediately before skin incision, at the end of surgery, 2 and 24 h after surgery for determination of plasma creatine kinase-MB (CK-MB) activity and cardiac troponin Ⅰ (cTnI) concentration. The adverse cardiovascular events were recorded. Results The incidences of ventricular premature beat, tachycardia, bradycardia, ventricular fibrillation and S-T segment elevation ( ＞0.1 mV) during surgery and the plasma CK-MB activity and cTnI concentration after surgery were significantly higher in group S than in group Ⅰ ( P ＜ 0.05). Conclusion Isoflurane has better myocardial protective effect than sevoflurane in patients undergoing OPCABG.     

异氟醚预先给药对缺氧复氧诱发人脐静脉内皮细胞多配体蛋白聚糖-1脱落的影响

目的 探讨异氟醚预先给药对缺氧复氧诱发的人脐静脉内皮细胞(HUVECs)多配体蛋白聚糖-1脱落的影响.方法 HUVECs培养于EMB-2培养液,采用随机数字表法,将其随机分为3组(n=32),正常对照组(C组):密闭箱内通入5%CO295%O2混合气体30 min,在正常氧浓度下继续培养;缺氧,复氧组(H/R组)置于氧浓度为1%缺氧培养箱内孵育4 h后,置于正常氧浓度的培养箱复氧2 h;异氟醚预先给药组(I组):密闭箱内通入1.73%异氟醚,30 min后行细胞缺氧复氧,方法同H/R组.缺氧复氧结束时测定HUVECs多配体蛋白聚糖-1表达、培养液脱落多配体蛋白聚糖-1浓度、细胞渗透性和细胞活力.结果 与C组比较,H/R组和Ⅰ组培养液脱落多配体蛋白聚糖-1浓度和细胞渗透性升高,HUVECs多配体蛋白聚糖-1表达水平和细胞活力降低(P＜0.01);与H/R组比较,Ⅰ组培养液脱落多配体蛋白聚糖-1浓度和细胞渗透性降低,HUVECs多配体蛋白聚糖-1表达水平和细胞活力升高(P＜0.01).结论 异氟醚预先给药可通过抑制HUVECs多配体蛋白聚糖-1的脱落,从而减轻HUVECs缺氧复氧损伤.

Abstract：

Objective To investigate the effect of isoflurane pretreatment on hypoxia/reoxygenation (H/R)-induced syndecan-1 shedding from human umbilical vein endothelial cells (HUVECs) . Methods HUVECs were cultured in EMB-2 medium and randomly divided into 3 groups ( n = 32 each) : control group (group C), H/R group and isoflurane pretreatment group (group I). H/R was produced by 4 h exposure of HUVECs to hypoxia followed by 2 h reoxygenation in H/R and I groups. HUVECs were exposed to the mixture of 5% CO2 and 95% O2 for 30 min and then cultured in normal culture atmosphere (21% O2) in group C. In group I, HUVECs were expased to 1.73% isoflurane and incubated for 30 min before H/R. The syndecan-1 expression, concentrations of shed syndecan-1 in the medium, and cell permeability and viability were measured at the end of reoxygenation. Results Compared with group C, the shed syndecan-1 concentration in the medium and cell permeability were significantly increased, while the syndecan-1 expression and cell viability decreased in H/R and Ⅰ groups ( P ＜ 0.01) . Compared with group H/R, the shed syndecan-1 concentration in the medium and cell permeability were significantly decreased, while the syndecan-1 expression and cell viability increased in group Ⅰ (P ＜ 0.01) . Conclusion Isoflurane pretreatment can protect HUVECs against H/R injury through inhibiting the syndecan-1 shedding.     

JNK信号通路在异氟醚预处理和七氟醚预处理减轻大鼠海马脑片缺氧无糖损伤中的作用

目的 评价c-Jun氨基末端激酶(JNK)信号通路在异氟醚预处理和七氟醚预处理减轻大鼠海马脑片缺氧无糖(OGD)损伤中的作用.方法雄性成年SD大鼠,体重270～290 g,断头处死,剥离海马,制备海马脑片.取大鼠海马脑片96张,采用随机数字表法,将其随机分为8组(n=12):对照组(C组)、OGD组、异氟醚预处理组(Iso组)、七氟醚预处理组(Sevo组)、SP600125+异氟醚预处理组(SP+Iso组)、SP600125+七氟醚预处理组(SP+Sevo组)、二甲基亚砜(DMSO)+异氟醚预处理组(DMSO+Iso组)和DMSO+七氟醚预处理组(DMSO+Sevo组).采用电生理技术,细胞外记录CA1区群锋电位(PS)波幅,计算PS恢复程度.采用碘化丙啶染色法,测定细胞活力.结果 与C组比较,其余各组PS恢复程度和细胞活力降低(P＜0.01);与OGD组比较,Iso组、Sevo组、SP+Iso.组、SP+Sevo组、DMSO+Iso组和DMSO+Sevo组PS恢复程度和细胞活力升高(P＜0.01);与180组比较,SP+Iso组PS恢复程度和细胞活力升高(P＜0.01),DMSO+Iso组PS恢复程度和细胞活力差异无统计学意义(P＞0.05);与Sevo组比较,SP+Sevo组PS恢复程度和细胞活力升高(P＜0.01),DMSO+Sevo组PS恢复程度和细胞活力差异无统计学意义(P＞0.05).结论 异氟醚预处理和七氟醚预处理可通过抑制JNK信号通路,减轻大鼠海马脑片缺氧无糖损伤.

Abstract：

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in the protective effect of isoflurane preconditioning and sevoflurane preconditioning against oxygen-glucose deprivation (OGD) injury in rat hippocampal slices. Methods Male adult SD rats weighing 270-290 g were anesthetized with ether and decapitated. The hippocampi were removed and sagittally sliced (400 μm thick) and placed in artificial cerebral spinal fluid aerated with 95% O2-5% CO2 . Ninety-six hippocampal slices were randomly divided into 8 groups (n = 12 each): control group (group C), OGD group, isoflurane preconditioning group (group Iso),sevoflurane preconditioning group (group Sevo) , SP600125 + isoflurane preconditioning group (group SP + Iso),SP600125 +sevoflurane preconditioning group (group SP + Sevo), DMSO + isoflurane preconditioning group (group DMSO + Iso) and DMSO + sevoflurane preconditioning group (group DMSO + Sevo). Electrophysiological technique was used to record the amplitude of population spike ( PS) in the stratum pyramidale of CA1 region and the degree of recovery of PS was calculated. The cell viability was determined by propidium iodide staining. Results Compared with group C, the degree of recovery of PS and cell viability were significantly decreased in the other groups ( P ＜ 0.01) . Compared with group OGD, the degree of recovery of PS and cell viability were significantly increased in groups Iso, Sevo, SP+Iso, SP+Sevo, DMSO+ Iso and DMSO + Sevo (P＜ 0.01). Compared with group Iso, the degree of recovery of PS and cell viability were significantly increased in group SP+Iso ( P ＜ 0.01) , while no significant change was found in group DMSO + Iso ( P ＞ 0.05) . Compared with group Sevo, the degree of recovery of PS and cell viability were significantly increased in group SP + Sevo ( P ＜ 0.01) , while no significant change was found in group DMSO + Sevo ( P ＞ 0.05). Conclusion Isoflurane preconditioning and sevoflurane preconditioning can attenuate the OGD injury to rat hippocampal slices through inhibiting JNK signaling pathway.     

异氟醚麻醉对新生大鼠海马激活肌细胞增强因子2信号通路的影响

目的 探讨异氟醚麻醉对新生大鼠海马激活肌细胞增强因子2(MEF2)信号通路的影响.方法 取出生5 d的SD大鼠24只,雌雄不拘,体重10～13 g,采用随机数字表法,将大鼠随机分为2组(n=12):对照组(C组)和异氟醚组(I组).I组大鼠放置在密闭箱中,吸人1.5%异氟醚和纯氧,吸入时间6 h,C组不做任何处理.于异氟醚麻醉2、4、6 h和麻醉结束后24 h(T1-4)时(C组于相应时点)分别取3只大鼠,断头处死,取海马组织,采用RT-PCR法测定MEF2mRNA、synGAPⅠ mRNA和Arc mRNA及突触素Ⅰ mRNA的表达水平,采用Westrn blot法测定突触素Ⅰ蛋白的表达水平.结果 与C组比较,I组T1-3时海马MEF2mRNA、synGAP Ⅰ mRNA、Arc mRNA和突触素Ⅰ mRNA、T2-4时海马突触素Ⅰ蛋白表达水平均上调(P＜0.05).结论 吸入麻醉浓度的异氟醚可能通过激活新生大鼠海马MEF2信号通路从而影响发育期突触的形成.

Abstract：

Objective To investigate the effects of isoflurane anenthesia on myocyte enhancer factor 2(MEF2) signaling pathway in neonatal rat hippocampus. Methods Twenty-four 5-day-old SD rats of both sexes,weighing 10-13 g, were randomly divided into 2 groups ( n = 12 each): control group (group C) and isoflurane group (group I). In group I, 1.5% isoflurane in 100% O2 was inhaled for 6 h. Group C received no treatment.Three rata in each group were sacrificed at 2, 4, 6 h of isoflurane anenthesia and 24 h after isoflurane anenthesia (T1-4), and the hippocampi removed for determination of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsinⅠ mRNA expression (by PT-PCR) and synapsin Ⅰ protein expression (by Western blot).Results Compared with group C, the expression of MEF2 mRNA, synGAP Ⅰ mRNA, Arc mRNA and synapsin Ⅰ mRNA at T1-3 and synapsin Ⅰ protein at T2-4 was up-regulated in group I ( P ＜ 0.05). Conclusion Inhalation of anaesthetic concentration of isoflurane may affect synapse formation during the development of central nervous system by actirating hippocampal MEF2 signaling pathways in neonatal rats.     

Effect of aging on expression of nitric oxide synthase I and activity of nitric oxide synthase in rat penis

Aim: To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of NOS in rat penis. Methods: Sixty male rats from 3 age groups (adult, old and senescent) were investigated. The expression of NOS I protein and mRNA in rat penis were detected by Western blot and RT-PCR respectively and the NOS activity, with ultraviolet spectrophotometry. Results: In the old and senescent group, NOS I protein expression was significantly decreased as compared with the adult. NOS I mRNA expression was well correlated with the protein expression. NOS activity was not statistically different between the adult and old groups, but it was significantly reduced in the senescent compared with the adult group (P<0.01). Conclusion: The aging-induced decreases in NOS I expression and NOS activity may be one of the main mechanisms leading to erectile dysfunction in the senescent rats.     

Effect of Radix Paeoniae Rubra on the expression of HO-1 and iNOS in rats with endotoxin-induced acute lung injury

Objective: To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase (HO-1) and induced nitric oxide synthase (iNOS) in endotoxin-induced acute lung injury in rats and its protective mechanism. Methods: Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group (NS group), lipopolysaccharide group ( LPS group), RPR-treatment group, RPR-prevention group and Hemin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, malondialdehyde ( MDA ) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemitry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope. Results: Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P<0.01). In RPR-treatment, RPR-prevention , and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P<0.05). The protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P<0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P<0.01); these parameters of lung injury however, were significantly lower in RPR-treatment. RPR-prevention, and Hemin groups than LPS group (P<0. 05 or P< 0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group. Conclusions: The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on lipopolysaccharide-induced acute lung injury is related to the inhibition of iNOS expression and the induction of HO-1 expression.     

脊髓神经激肽-1受体在吸入麻醉药对小鼠抗伤害性效应中的作用

目的 探讨脊髓神经激肽-1受体(NK-1R)在吸入麻醉药对小鼠抗伤害性效应中的作用.方法 昆明种小鼠320只,雌雄各半,体重20～25g,按分层随机区组设计,将小鼠随机分为4组(n=80):生理盐水组(NS组)、恩氟醚组(E组)、异氟醚组(Ⅰ组)和七氟醚组(S组),每组再分为4个亚组,Ⅰ组～Ⅳ组,每亚组20只.NS组腹腔注射生理盐水1.0 ml/kg,E组、Ⅰ组和S组分别腹腔注射恩氟醚0.5 ml/kg、异氟醚0.4 ml/kg和七氟醚2.0 ml/kg,腹腔注射结束后5 min时,Ⅰ组～Ⅳ组分别鞘内注射生理盐水5μl、Sar-SP(NK-1R激动剂)20、40和80ng.于腹腔给药前(基础状态)、鞘内给药后测定甩尾潜伏期(TFL),于鞘内给药后1 min时行福尔马林实验,记录Ⅰ相和Ⅱ相累积舔足时间(PLT).结果 与NS组比较,E组、Ⅰ组和S组相应亚组TFL延长,Ⅰ相和Ⅱ相PLT缩短(P＜0.05或0.01);与Ⅰ组比较,E组、Ⅰ组和S组各其余亚组TFL缩短(P＜0.05);E组、Ⅰ组和S组的Ⅱ组～Ⅳ组TFL均逐渐缩短(P＜0.05);NS组、E组、Ⅰ组和S组各亚组间Ⅰ相和Ⅱ相PLT比较差异无统计学意义(P＞0.05).结论 脊髓 NK-1R与吸入麻醉药(恩氟醚、异氟醚、七氟醚)抗热刺激诱发的伤害效应有关,与其抗化学性刺激和炎性刺激诱发的伤害效应无关.

Abstract：

Objective To investigate the role of neurokinin-1 receptor (NK-1R) in the anti-nociceptive effect of enflurane, isoflurane and sevoflurane in mice. Methods Three hundred and twenty Kunming mice of both sexes weighing 20-25 g were randomly divided into4 groups (n =80 each): group normal saline (group NS);group enflurane (group E); group isoflurane (group I) and group sevoflurane (group S). Normal saline (NS) 1.0ml/kg, erflurane 0.5 ml/kg, isoflurane 0.4 ml/kg and sevoflurane 2.0 ml/kg were injected intraperitoneally in NS,E,I and S groups respectively. Each group was further divided into 4 subgroups receiving intrathecal NS 5 μl and Sar-SP (NK-IR agonist) 20, 40 and 80 ng respectively at 5 min after intraperitoneal injection of inhalation anesthetics. The anti-nociceptive effect of the inhalation anesthetics was assessed by tail flick latency (TFL) (the latency for removal of the tail from the path of heat source) and paw-licking time (PLT) after intraplantar formalin injection. Results lntraperitoneal enflurane, isoflurane and sevoflurane significantly prolonged TFL and shortened PLT. Intrathecal Sar-SP 20, 40 and 80 ng significantly shortened TFL dose-dependently but had no significant effeet on PLT as compared with control subgroup. Conclusion NK-1R is involved in the anti-nociceptive effect of enflurane, isoflurane and sevofluran on thermal pain but not chemical and inflammatory pain.     

肉毒毒素A对大鼠皮肤及创面组织中SP、CGRP、TGF-β1和α-SMA的影响

Objective To investigate the effect of botulinum toxin type A (Botox A) injection on hypertrophic scar in rabbit ear model. Methods The hypertrophic scar model was established in 16 Japanese rabbits' ears. These wounds were divided into two groups as group T(treated with Botox A, n =48) and group S (not treated, n = 48). The wounds healing times and scar hypertrophy were observed with 8 specimen of normal skin at the rabbit ears as sham group B. HE stain was used to assess the hypertrophic index(HI). The expression of collagen Ⅰ and Ⅲ was tested by western-blot. The cell cycle of fibroblasts was studied by flow cytometry. Results The [] was significantly lower in group T than in group S(P < 0.01). The expression of collagen Ⅰ and Ⅲ, as well as the ratio of Ⅰ to Ⅲ, was markedly stronger in group S than in group T(P < 0.01). Compared with group T, more fibroblasts were in G2-M in gToup S and fewer in G0-G1 (P <0.05). Conclusions Local injection of Botox A can inhibite the formation of hypertrophic scar and the activity of fibroblasts in rabbit ear model. It can significantly decrease the expression of collagen Ⅰ and Ⅲ in hypertrophic scar, as well as the ratio of collagen Ⅰ to Ⅲ. It serves as the basis for the treatment of hypertrophic scar with Botox A.     

A型肉毒毒素局部应用对兔耳增生性瘢痕创面愈合和瘢痕增生的影响

Objective To investigate the effect of botulinum toxin type A (Botox A) injection on hypertrophic scar in rabbit ear model. Methods The hypertrophic scar model was established in 16 Japanese rabbits' ears. These wounds were divided into two groups as group T(treated with Botox A, n =48) and group S (not treated, n = 48). The wounds healing times and scar hypertrophy were observed with 8 specimen of normal skin at the rabbit ears as sham group B. HE stain was used to assess the hypertrophic index(HI). The expression of collagen Ⅰ and Ⅲ was tested by western-blot. The cell cycle of fibroblasts was studied by flow cytometry. Results The [] was significantly lower in group T than in group S(P < 0.01). The expression of collagen Ⅰ and Ⅲ, as well as the ratio of Ⅰ to Ⅲ, was markedly stronger in group S than in group T(P < 0.01). Compared with group T, more fibroblasts were in G2-M in gToup S and fewer in G0-G1 (P <0.05). Conclusions Local injection of Botox A can inhibite the formation of hypertrophic scar and the activity of fibroblasts in rabbit ear model. It can significantly decrease the expression of collagen Ⅰ and Ⅲ in hypertrophic scar, as well as the ratio of collagen Ⅰ to Ⅲ. It serves as the basis for the treatment of hypertrophic scar with Botox A.     

手术对异氟醚麻醉下老龄大鼠术后认知功能的影响

目的 探讨手术对老龄大鼠异氟醚麻醉下术后认知功能的影响.方法 健康雄性老龄SD大鼠72只,年龄20月,体重500～600 g,随机分为3组(n=24):对照组(C组)、异氟醚麻醉组(I组)和手术组(O组).C组吸入30%氧气2 h,I组吸入1.5%异氟醚和30%氧气的混合气体2 h,O组吸入1.5%异氟醚和30%氧气的混合气体2 h,并实施腹部手术.于麻醉结束后或术后24 h时随机取8只大鼠,取海马组织,采用免疫组织化学法和RT-PCR法分别测定神经元胆碱乙酰转移酶(ChAT)及ChAT mRNA的表达水平,其余大鼠进行Morris水迷宫实验,测定认知功能.结果 与C组比较,I组和O组逃避潜伏期延长,原平台象限停留时间缩短,穿越原平台次数减少,海马神经元ChAT mRNA及其蛋白表达水平降低(P<0.05);与I组比较,O组术后第4、5天逃避潜伏期延长,原平台象限停留时间缩短,海马神经元ChAT mRNA及其蛋白表达水平降低(P<0.05);与麻醉结束后或术后第3天比较,C组第4、5天逃避潜伏期差异无统计学意义(P>0.05),I组和O组逃避潜伏期延长(P<0.05);I组和O组麻醉结束后或术后第4、5天逃避潜伏期差异无统计学意义(P>0.05).结论 手术操作可加重异氟醚引起的老龄大鼠术后认知功能障碍,其机制可能与海马胆碱能神经元受损有关.     

吸入不同浓度异氟醚对老龄大鼠海马细胞色素c表达的影响

目的 评价吸入不同浓度异氟醚对老龄大鼠海马细胞色素c(Cyt c)表达的影响.方法 健康雄性老龄SD大鼠63只,月龄20月,体重500～600 g,随机分为3组(n=21),对照组(C组):吸入30%氧气2 h;0.75%异氟醚组(L组):吸入0.75%异氟醚和30%氧气的混合气体2 h;1.5%异氟醚组(I2组):吸入1.5%异氟醚和30%氧气的混合气体2 h.分别于麻醉30 min、1和2 h时,各组取5只大鼠,取动脉血样行血气分析.于麻醉结束后24 h时,各组取8只大鼠,测定认知功能;取8只大鼠,分别采用免疫组化法和Western blot法测定海马Cyt c 的表达水平.结果 与C组比较,Ⅰ1组和Ⅰ2组逃避潜伏期延长,原平台象限停留时间缩短,穿越原平台次数减少,海马Cyt c表达上调(P＜0.05);与Ⅰ1组比较,Ⅰ2组逃避潜伏期、原平台象限停留时间缩短和穿越原平台次数差异无统计学意义(P＞0.05),海马Cyt c表达上调(P＜0.05).结论 吸入异氟醚可通过上调海马Cyt c的表达导致老龄大鼠认知功能障碍.     

异氟醚对老龄大鼠海马CA3区突触素表达的影响

目的 评价异氟醚对老龄大鼠海马CA3区突触素表达的影响.方法 雌性清洁级SD大鼠63只,月龄24月,体重400～650 g,随机分为3组(n=21):对照组(C组)、1.2%异氟醚组(E_1组)和1.8%异氟醚组(E_2组).C组吸入含40%氧气的空氧混合气体3 h;E_(1,2)组吸入3%异氟醚行麻醉诱导,待翻正反射消失后再分别吸入1.2%、1.8%异氟醚维持3 h.各组随机取12只大鼠,于麻醉结束后第1天采用Morris水迷宫系统测定大鼠认知功能(逃避潜伏期和探索时间),连续测定7 d;随机取9只大鼠于麻醉结束后第1、3和7天处死,测定海马CA3区突触素的表达水平.结果 与C组比较,E_1组和E_2组麻醉结束后第2、3天逃避潜伏期延长(P<0.05或0.01),第4～6天逃避潜伏期差异无统计学意义(P>0.05),麻醉结束后海马CA3区突触素表达持续下调(P<0.05).三组探索时间比较差异无统计学意义(P>0.05);与E_1组比较,E_2组逃避潜伏期差异无统计学意义(P>0.05),海马CA3区突触素表达下调(P<0.01).结论 异氟醚致老龄大鼠认知功能障碍与海马突触素表达无关.     

异氟醚对大鼠海马蛋白激酶A和蛋白激酶C水平的影响

目的 评价异氟醚对大鼠海马蛋白激酶A(PKA)和蛋白激酶C(PKC)水平的影响.方法 健康雄性SD大鼠36只,月龄3月,体重180～220g,随机分为3组(n=12),Ⅰ组不给予任何处理,直接进行认知功能测试;Ⅱ组吸入1.2%异氟醚4 h,2 d后进行认知功能测试;Ⅲ组吸入1.2%异氟醚4 h,2周后进行认知功能测试.采用Morris水迷宫进行大鼠认知功能测试,记录逃避潜伏期.认知功能测试完毕后,处死大鼠,取海马,测定PKA和PKC的表达和活性.结果 与Ⅰ组比较,Ⅱ组逃避潜伏期差异无统计学意义(P＞0.05),Ⅲ组逃避潜伏期延长,Ⅱ组和Ⅲ组海马PKA和PKC的表达下调,活性降低(P＜0.05);与Ⅱ组比较,Ⅲ组逃避潜伏期延长(P＜0.05),海马PKA和PKC的表达和活性差异无统计学意义(P＞0.05).结论 吸入1.2%异氟醚4 h可抑制海马PKA和PKC的水平,从而导致大鼠认知功能障碍.     

异氟醚对老年大鼠脑组织神经元凋亡的影响

目的 探讨异氟醚对老年大鼠脑组织神经元凋亡的影响.方法 健康雌性老年SD大鼠90只,月龄22～24月,体重497～593 g,随机分为对照组(C组)、1.2%异氟醚组(Ⅰ1组)和1.8%异氟醚组(Ⅰ2组),每组30只.C组吸入含40%O2的空氧混合气体3 h;Ⅰ1组和Ⅰ2组分别吸入1.2%、1.8%异氟醚3 h维持麻醉.待翻正反射消失时各组随机取3只大鼠股动脉置管监测血液动力学,于股动脉置管后5 min、吸入异氟醚1、2、3 h时抽股动脉血行血气分析;大鼠苏醒后24 h时各组随机取12只行Morris水迷宫实验测试认知功能,历时7 d,记录逃避潜伏期;分别于苏醒后24、72 h及7 d时各组随机取5只大鼠断头处死取脑,采用TUNEL法检测海马及皮层区凋亡神经元,计算神经元凋亡率.结果 三组各时点血液动力学指标及血气分析结果 差异无统计学意义(P>0.05);与C组比较,Ⅰ1组和Ⅰ2组第2、3天逃避潜伏期延长(P<0.05或0.01),第4～6天差异无统计学意义(P>0.05),苏醒后24、72 h及7 d时皮层区神经元凋亡率升高(P<0.05或0.01).结论 吸入异氟醚可导致老年大鼠认知功能一过性降低,可能与其诱发大脑皮层区神经元凋亡有关.     

吸入七氟醚对不同性别大鼠长期认知功能的影响

目的 评价吸入七氟醚对不同性别大鼠长期认知功能的影响.方法 健康成年SD大鼠42只,雌性大鼠22只(体重180～220 g),采用随机数字表法,将其随机分为2组(n=11):雌性对照组(Fc组)和雌性麻醉组(Fs组),雄性大鼠20只(体重380～440 g),采用随机数字表法,将其随机分为2组(n=10):雄性对照组(Mc组)和雄性麻醉组(Ms组).Fs组和Ms组吸入3%七氟醚2 h,Fc组和Mc组吸入95%氧气2 h,氧流量4 L/min.分别于停止给药后1、30、60、90 d时进行自发活动实验;分别于停止给药后2、30、60、90 d时进行避暗实验;分别于停止给药后3～7 d、31～35 d、61～65 d和91～95d时进行Morris水迷宫实验.结果 与Fc组比较,Fs组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3、31 d时逃避潜伏期和游泳总路程延长(P<0.05).与Mc组比较,Ms组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3～6 d、31～34 d、61 d时逃避潜伏期和游泳总路程延长(P<0.05).与Fs组比较,Ms组停止给药后4～6 d、34 d时逃避潜伏期和,游泳总路程延长(P<0.05).结论 吸入七氟醚可导致大鼠长期认知功能障碍,且对雄性大鼠的影响更明显.     

吸入七氟醚对不同性别大鼠长期认知功能的影响

目的 评价吸入七氟醚对不同性别大鼠长期认知功能的影响.方法 健康成年SD大鼠42只,雌性大鼠22只(体重180～220 g),采用随机数字表法,将其随机分为2组(n=11):雌性对照组(Fc组)和雌性麻醉组(Fs组),雄性大鼠20只(体重380～440 g),采用随机数字表法,将其随机分为2组(n=10):雄性对照组(Mc组)和雄性麻醉组(Ms组).Fs组和Ms组吸入3%七氟醚2 h,Fc组和Mc组吸入95%氧气2 h,氧流量4 L/min.分别于停止给药后1、30、60、90 d时进行自发活动实验;分别于停止给药后2、30、60、90 d时进行避暗实验;分别于停止给药后3～7 d、31～35 d、61～65 d和91～95d时进行Morris水迷宫实验.结果 与Fc组比较,Fs组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3、31 d时逃避潜伏期和游泳总路程延长(P<0.05).与Mc组比较,Ms组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3～6 d、31～34 d、61 d时逃避潜伏期和游泳总路程延长(P<0.05).与Fs组比较,Ms组停止给药后4～6 d、34 d时逃避潜伏期和,游泳总路程延长(P<0.05).结论 吸入七氟醚可导致大鼠长期认知功能障碍,且对雄性大鼠的影响更明显.

Abstract：

Objective To explore the difference in the effect of isoflurane inhalation on long-term cognitive function between male and female rate.Methods Forty-two SD rats (22 female, 20 male) that exhibited normal spontaneous activity and behaved normally in passive avoidance and Morris water maze tests were used in this study. They were divided into 2 sex groups:group female (group F) and group male (group M). Each group was further divided into 2 subgroups: control subgroup (Fc, Mc groups) and isoflurane group (Fs, Ms groups). The animals were anesthetized with 3 % isoflurane in O2 for 2 h in the 2 study subgroups, while the control subgroups inhaled O2 for 2 h. The spontaneous activity test was performed at 1, 30, 60 and 90 d, while the passive avoidance task was performed at 2, 30, 60 and 90 d after isoflurane anesthesia. Morris water maze test was performed for 5 consecutive days at 3-7 d, 31-35 d, 61-65 d, and 91-95 d after isoflurane anesthesia.Results In spontaneous activity test the total distance and the speed were significantly decreased at 1 d after isoflurane anesthesia in both Fs and Ms subgroups as compared with Fc and Mc subgroups. There was no significant difference in the number of error and latency after isoflurane anesthesia compared with the control subgroups in both male and female rats in the passive avoidance task. In Morris water maze test the escape latency and swimming distance were significantly prolonged at 1 and 31 d after isoflurane anesthesia as compared with control subgroup in female rats and at 3-6d, 31-34 d and 61 d after isoflurane anesthesia as compared with control subgroup in male rats, and were significantly longer after isoflurane anesthesia in male than in female rats. Conclusion Two hour 3.0% isoflurane anesthesia can impair long-term cognitive function and the impairment is greater in male than in female rats.     

吸入七氟醚对不同性别大鼠长期认知功能的影响

目的 评价吸入七氟醚对不同性别大鼠长期认知功能的影响.方法 健康成年SD大鼠42只,雌性大鼠22只(体重180～220 g),采用随机数字表法,将其随机分为2组(n=11):雌性对照组(Fc组)和雌性麻醉组(Fs组),雄性大鼠20只(体重380～440 g),采用随机数字表法,将其随机分为2组(n=10):雄性对照组(Mc组)和雄性麻醉组(Ms组).Fs组和Ms组吸入3%七氟醚2 h,Fc组和Mc组吸入95%氧气2 h,氧流量4 L/min.分别于停止给药后1、30、60、90 d时进行自发活动实验;分别于停止给药后2、30、60、90 d时进行避暗实验;分别于停止给药后3～7 d、31～35 d、61～65 d和91～95d时进行Morris水迷宫实验.结果 与Fc组比较,Fs组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3、31 d时逃避潜伏期和游泳总路程延长(P<0.05).与Mc组比较,Ms组停止给药后1 d时活动总路程缩短,平均速度减慢,停止给药后3～6 d、31～34 d、61 d时逃避潜伏期和游泳总路程延长(P<0.05).与Fs组比较,Ms组停止给药后4～6 d、34 d时逃避潜伏期和,游泳总路程延长(P<0.05).结论 吸入七氟醚可导致大鼠长期认知功能障碍,且对雄性大鼠的影响更明显.     

竹节参皂苷对异氟醚所致发育期大鼠神经毒性和认知功能的影响

目的探讨竹节参皂苷对异氟醚所致发育期大鼠海马神经毒性及认知功能的影响。方法 7日龄SD大鼠60只,雌雄不限,体重20~25g,随机分为四组(n=15)。对照组(Con组):吸入对照气(空气)6h;异氟醚组(Iso组):吸入1.8%异氟醚6h;竹节参皂苷+异氟醚组(Iso+ChIV组):麻醉前30min腹腔注射竹节参皂苷30mg/kg后吸入1.8%异氟醚6h;竹节参皂苷(ChIV组):麻醉前30min腹腔注射竹节参皂苷30mg/kg后吸入对照气(空气)6h。麻醉结束后12h取海马组织检测突触后致密蛋白95(PSD95)、突触素I(Synapsin I)、B淋巴细胞瘤2相关X蛋白(Bax)、B淋巴细胞瘤2(Bcl-2)蛋白含量,TUNEL染色检测神经元凋亡情况,测定乳酸脱氢酶(LDH)活性。于出生后第31~35天采用水迷宫评估空间学习记忆能力。结果与Con组比较,Iso组PSD95、Bcl-2蛋白含量明显降低,Bax蛋白含量明显升高,TUNEL阳性细胞数明显增多,LDH活性明显增强(P0.05);与Iso组比较,Iso+ChIV组PSD95、Bcl-2蛋白含量明显升高,Bax蛋白含量明显降低,TUNEL阳性细胞数明显减少,LDH活性明显减弱(P0.05)。与Con组比较,Iso组第34和35天逃避潜伏路线明显延长(P0.05),第33、34和35天逃避潜伏期明显延长(P0.05),第35天目标象限停留时间明显缩短,平台穿越次数明显减少(P0.05)。与Iso组比较,Iso+ChIV组第34和35天逃避潜伏路线明显缩短,逃避潜伏期明显缩短(P0.05),第35天目标象限停留时间明显延长,平台穿越次数明显增多(P0.05)。结论竹节参皂苷可明显改善异氟醚所致发育期大鼠神经毒性和认知功能,其机制可能与抑制发育期神经凋亡有关。     

七氟醚对老年大鼠术后认知功能及海马miR-132表达的影响

目的 探讨七氟醚对老年大鼠认知功能及海马miR-132表达的影响.方法 雄性SD大鼠60只,18～20月龄,行水迷宫训练5d后,按随机数字表法分为对照组(C组)和七氟醚组(S组),每组30只.S组2％七氟醚,C组纯氧处理后6h、1d、3d、7d进行水迷宫实验,记录逃避潜伏期和游泳总距离.各时点水迷宫实验结束后处死大鼠取海马组织,采用实时定量聚合酶链反应检测海马组织内miR-132的表达.结果 与C组比较,S组麻醉后6h、1d、3d、7d水迷宫测试的逃避潜伏期及游泳总距离明显延长,海马miR-132表达(0.41±0.03、0.43±0.04、0.51±0.03、0.62±0.05)明显降低(P＜0.05).S组内,与麻醉后6h比较,麻醉后1d及以后时间点水迷宫测试的逃避潜伏期[(69±10)、(61±11)、(43±9)s]明显缩短(P＜0.05);麻醉后3、7d水迷宫测试的游泳总距离[(1 424±198)、(1 052±134) cm]明显缩短(P＜0.05),海马miR-132的表达明显增加(P＜0.05).S组内,麻醉后7d与麻醉后各时间点比较,水迷宫测试的逃避潜伏期及游泳总距离明显缩短(P＜0.05),海马miR-132的表达明显增加(P＜0.05).结论 七氟醚可导致老龄大鼠术后认知功能障碍,其机制可能与其抑制海马组织内miR-132表达有关.