吗啡耐受小鼠脊髓突触素的变化

目的：观察氯胺酮抗吗啡耐受过程中对小鼠脊髓突触素的影响。方法：实验于2003-06／09在华中科技大学同济医学院附属同济医院麻醉学实验室完成。昆明种小鼠24只，随机分为4组（n=6）：对照组。皮下注射生理盐水（10mL／kg）30min后腹腔注射生理盐水（10mL／kg）；慢性吗啡耐受模型组，皮下注射吗啡（10mg/kg）30min后腹腔注射生理盐水（10mL／kg）；氯胺酮10mg／kg组：吗啡皮下注射30min后腹腔注射氯胺酮10mg／kg，（用前稀释成10mL／kg，以与对照组等容）；氯胺酮20mg／kg组：吗啡皮下注射30min后腹腔注射氯胺酮20mg／kg。各组每天重复用药两次，连续9d，隔天最后一次给药后1h，采用测触痛阈法测撤爪反应的机械触痛阈值作为疼痛指标。采用免疫组织化学，方法测定脊髓突触素免疫反应阳性产物在吗啡耐受过程中的变化。结果：在实验过程中无动物死亡，全部进入结果分析。①对照组在各时间点撤爪阈值无明显变化；慢性吗啡耐受模型组在第1、3天撤爪阈值与对照组在同时间点撤爪阈值相近，第5天至第9天撤爪阈值进一步下降。氯胺酮10mg／kg组撤爪阈值的变化趋势与慢性吗啡耐受模型组相同；氯胺酮20mg／kg组的撤爪阈值变化不明显，在各时间点与对照组相近，表明20mg／kg氯胺酮与吗啡合用均有部分抗吗啡耐受形成的作用。②在对照组小鼠脊髓中，脊髓背角Ⅰ-Ⅱ层突触素免疫阳性产物呈棕黄色颗粒状，分布在胞浆中；慢性吗啡处理后第9天慢性吗啡耐受模型组脊髓背角Ⅰ-Ⅱ层突触素免疫阳性产物表达较对照组明显密集；氯胺酮10mg／kg组突触素免疫阳性产物表达与慢性吗啡耐受模型组相比变化不明显；氯胺酮20mg／kg组脊髓背角Ⅰ-Ⅱ层突触素免疫阳性产物表达比慢性吗啡耐受模型组相比明显稀疏，与对照组相似。③慢性吗啡耐受模型组第9天脊髓突触素阳性产物吸光度值比对照组明显增加，可达35％，差异有显著性[（97&;#177;11），（72&;#177;9），P〈0．05[；氯胺酮10mg／kg组与慢性吗啡耐受模型组脊髓突触素阳性产物吸光度值接近，差异无显著性[（93&;#177;11），（97&;#177;11），P〉0．05]，而明显高于对照组，差异有显著性（P〈0．05）；氯胺酮20mg／kg组第9天突触素阳性产物吸光度值分别比慢性吗啡耐受模型组降低20％，差异有显著性[（78&;#177;7），（97&;#177;11），P〈0．05]，而与对照组相比，差异无显著性（P〉0．05）。表明20mg／kg氯胺酮可以显著降低小鼠耐受时脊髓突触素吸光度。结论：吗啡耐受的机制可能涉及脊髓突触素的上调，氯胺酮可能通过抑制脊髓突触素上调而具有部分抗吗啡耐受作用。     

突触素在糖尿病视网膜细胞表达改变的研究

目的探讨突触素(synaptophysin,SYN)在糖尿病视网膜病变(diabeticretinopathy,DR)发病中的作用。方法Sprague-Dawley雄性大鼠尾静脉注射链脲佐菌素造模,以血糖测定和尿糖水平测定进行筛选,正常对照组尾静脉注射等量枸橼酸钠缓冲液。成模后继续饲养4周,取出眼球视网膜组织,连续冰冻切片,用免疫组织化学SABC法染色观察各组大鼠视网膜SYN的表达情况。结果糖尿病大鼠成模前,两组动物的体重、血糖和尿糖检测结果间差异无统计学意义(P>0.05)。成模后4周,糖尿病组与正常组大鼠体重、血糖和尿糖分别为(189.13±18.41)g,(23.72±3.25)mmol/L,(++至+++)和(260.52±32.15)g,(4.95±0.52)mmol/L,(-),两组差异有统计学意义(P<0.01)。SYN在正常组大鼠视网膜节细胞层及内核层均有表达,正常组大鼠视网膜SYN的光密度值为96.31±15.34。糖尿病大鼠视网膜内SYN表达显著减弱,糖尿病大鼠视网膜SYN的光密度值为65.73±8.92。两组相比,差异有统计学意义(P<0.01)。结论SYN随糖尿病大鼠病程延长、病情加重,表达量减少。其表达量的变化很可能是DR发生、发展的重要因素。     

喂饲大豆磷脂酰胆碱幼年大鼠脊髓突触素的表达变化

目的：观察大豆磷脂酰胆碱对幼年大鼠脊髓前角内突触素表达的影响，探讨大鼠脊髓神经突触可塑性及大豆磷脂酰胆碱的作用途径。 方法：实验于2004—03／12在兰州大学基础医学院神经研究室完成。选择5周龄健康雄性Wistar大鼠22只，随机分为2组，大豆磷脂酰胆碱组和对照组各11只。大豆磷脂酰胆碱组大鼠给予大豆磷脂酰胆碱500mg／（kg&;#183;d），溶于50mL双蒸水灌胃，1次／d。对照组大鼠等量双蒸水，灌胃，1次／d。每3天测1次体质量，大豆磷脂酰胆碱剂量随体质量变化相应调整，共喂养8周。喂养8周后，两组大鼠均用水合氯醛腹腔注射麻醉。灌注固定，取胸段脊髓中段和腰膨大最粗处经石蜡包埋后进行连续切片，进行免疫组化法染色。测量胸段和腰膨大脊髓灰质前角区各视野突触素的免疫反应阳性产物灰度值，被测区突触素含量越高，免疫染色越深，则灰度值越小，反之越大。 结果：22只大鼠全部进入结果分析，无脱失。①大豆磷脂酰胆碱组大鼠胸段和腰膨大脊髓灰质前角区突触素的免疫反应阳性产物染色较深，呈棕黄色阳性颗粒，胸段和腰膨大脊髓突触素灰度值均显著小于对照组[221．50&;#177;2．18，239．14&;#177;1．90；238．33&;#177;2．12，256．36&;#177;2．20（t=5．525，4．892，P〈0．01）1。②两组大鼠胸段前角突触素灰度值均显著小于腰膨大灰度值（t=5．918，5．375，P〈0．01）。 结论：幼年大鼠经大豆磷脂酰胆碱喂饲后，脊髓突触素的免疫表达增强，提示大豆磷脂酰胆可以提高幼年大鼠脊髓神经突触可塑性，而且胸段脊髓的突触可塑性强于腰膨大。     

在脊髓水平拮抗黑皮素受体可以抑制吗啡耐受

长期使用吗啡总会引发耐受，这是阿片治疗中的一大问题。最近的研究已经证明黑皮素（melanocortin）受体的配基对阿片效应可能有调节作用，但它是否影响吗啡的耐受过程还不清楚。为了解决这一问题，波兰的Katarzyna Starowicz等利用甩尾实验模型研究了蛛网膜下腔注射黑皮素3、4受体的非特异性拮抗剂SHU9119和黑皮素4受体的特异拮抗剂JKC-363对吗啡耐受的影响。结果表明，在吗啡用药的同时联合使用SHU9119或JKC-363能显著延缓吗啡耐受的进程。     

吗啡对大鼠海马神经元突触传递的作用及机制

目的：从离子通道角度研究吗啡对中枢神经系统兴奋性及抑制性突触传递的作用，以探讨吗啡镇痛机制。方法：原代培养新生Wistar大鼠的海马神经元。采用膜片钳技术研究吗啡对其兴奋性及抑制性突触后电流及谷氨酸诱发电流的影响。结果：①吗啡可明显增强海马神经元兴奋性突触传递，加吗啡后自发兴奋性突触后电流发放频率增加了207．8％(t=42．1828，P&;lt;0．01)。此作用可被阿片受体阻断剂纳洛酮阻断；②吗啡对微小兴奋性突触后电流的发放频率及谷氨酸诱发电流的幅度没有明显影响(t=0．962，t=0．791，P&;gt;0．05)；③吗啡可明显抑制神经元自发抑制性突触后电流，纳洛酮可拮抗吗啡作用(P&;lt;0．01)。结论：吗啡对海马神经元的兴奋作用不是由于吗啡直接作用于兴奋性氨基酸-谷氨酸突触传递过程，而是可能由于抑制了抑制性中间神经元，间接产生的兴奋达到镇痛作用。     

突触素与慢性脑缺血的研究进展

慢性脑缺血（chroni ccerebral ischemia,CCI）与临床许多脑血管疾病密切相关,是多种原因引发的长期慢性脑血流灌注不足导致的以持久或进展性认知功能障碍为主要表现的一组疾病。还是血管性痴呆、Alzheimer病及Binswanger病等多种疾病的共同病理基础,其主要的病理学改变包括皮质萎缩、皮质和海马神经元变性、白质疏松、神经胶质细胞增生和毛细血管床的改变等。     

缺氧缺血脑损伤大鼠脑神经结构与突触素表达的变化

目的 研究大鼠缺氧缺血性脑损伤（HIBD）后脑神经结构与突触素表达的变化.方法 将7日龄SD大鼠分为HIBD组和假手术对照组.采用单侧颈总动脉结扎术建立缺氧缺血性脑损伤大鼠模型,于脑缺氧缺血后1,4,7,14,28 d采集脑组织标本,进行HE染色和透射电镜观察其组织病理学及神经超微结构变化,并用免疫组化技术检测大鼠脑皮质及海马CA1区突触素的表达.结果 HIBD组脑损伤后神经元突起呈灶性坏死,突触数量减少、结构破坏;同时突触素的表达逐渐增高,至7 d达到高峰;而后开始下降,至28 d明显低于相应对照组（P〈0.001）.假手术对照组突触素表达水平则随日龄增加逐渐增高（P〈0.001）.结论 缺氧缺血性脑损伤可影响发育期脑组织神经结构与突触素的表达,损伤后两周内脑神经具有较强的突触可塑性.     

Cajal间质细胞及突触素在先天性巨结肠病变肠段中的分布

目的:探讨Cajal间质细胞(ICCs)及突触素(SY)在先天性巨结肠发病中的作用.方法:应用免疫组化PV法对10例对照者和32例先天性巨结肠患儿肠标本ICCs、SY进行检测.结果:在对照组及巨结肠有神经节细胞段,ICCs大量分布在肌层内及肌间神经丛周围,并形成网络结构.肌间神经丛、纵肌层、环肌层、黏膜肌层均可见大量SY免疫反应阳性产物.在无神经节细胞段,肠壁各层ICCs细胞密度明显减少甚至消失,正常所见的网络结构遭到破坏.肌间神经丛、黏膜下、环肌层、纵肌层SY表达均不同程度地减少.结论:ICCs、SY分布异常是先天性巨结肠病理改变之一,可能是该病重要的发病机制,参与肠运动障碍的发生.     

褪黑素对吗啡依赖小鼠肾损害的治疗作用

目的：探讨褪黑素对吗啡依赖小鼠肾组织损害的治疗作用。方法：用皮下定量注射吗啡的方法建立吗啡依赖小鼠模型,经褪黑素治疗4周后,用HE染色,酶组织化学染色及图像分析方法,在光镜下观察吗啡依赖小鼠肾脏组织结构及酶组织化学变化。结果：肾细胞变性的发生率在吗啡自然戒断组为10例（10／10）;ACP,活性升高,而SDH活性降低。褪黑素治疗组仅1例（1／10）,且为个别肾细胞水肿;ACP,和SDH活性正常。结论：褪黑素可使吗啡所致的肾损害得到良好恢复。     

肿瘤坏死因子α在吗啡依赖和戒断大鼠海马CA1区的表达变化

目的：探讨吗啡依赖和戒断大鼠海马CA1区肿瘤坏死因子α的表达变化。方法：实验于2004—04／2005—03在泸州医学院组织胚胎学实验室完成。实验动物选择普通级两三月龄雄性SD大鼠24只。按随机数字法将实验动物分为4组：对照组、吗啡依赖组和盐酸纳洛酮催促戒断1h组和戒断3h组（后两组合称戒断组），每组6只。采用剂量递增法建立吗啡依赖动物模型，用纳洛酮催促吗啡依赖动物戒断反应。具体方法为每天两次在大鼠背部皮下注射盐酸吗啡，首日10mg／kg，隔日每次增加10mg／kg，至第6天末次注射50mg／kg。吗啡依赖组末次注射后6h麻醉下灌注固定。盐酸纳洛酮催促戒断组大鼠于末次注射吗啡6h后，以盐酸纳洛酮5mg／kg皮下注射激发戒断症状，1h和3h后，同吗啡依赖组处理实验动物。对照组大鼠按照同期平行对照的原则，以相同方式注射同体积的生理盐水。记录大鼠在正常及实验状态下的活动状况。同时取大鼠海马CA1区分别作苏木精一伊红和肿瘤坏死因子α免疫组织化学，测免疫反应阳性细胞的数量和吸光度。结果：整个实验过程未出现大鼠异常死亡，吗啡注射的所有动物均成功建立吗啡依赖动物模型，全部进入结果分析。①海马形态改变：吗啡依赖和戒断大鼠海马CA1区出现结构松散、神经元萎缩和坏死等改变。②肿瘤坏死因子α蛋白表达：对照组大鼠海马CA1区肿瘤坏死因子α蛋白表达轻度阳性，吗啡依赖组和戒断组肿瘤坏死因子α阳性细胞数均增加，各组阳性细胞主要是胶质细胞和神经元。各组阳性细胞均数与对照组比较，差异均有统计学意义[（34．83&;#177;3.54），（17．50&;#177;2．88），P〈0．01]；[（38．83&;#177;4．62），（17．50&;#177;2．88），P〈0．01]；[（58．17&;#177;6．62），（17．50&;#177;2．88），P〈0．01]。而吗啡依赖组与盐酸纳洛酮催促戒断3h组差异无统计学意义[（34．83&;#177;3．54），（38．83&;#177;4．62），P〉0．05]。吗啡依赖组和戒断组肿瘤坏死因子α阳性细胞吸光度增加，各组阳性细胞吸光度均数与对照组比较差异也均有统计学意义[（0．3780&;#177;0．0094），（0．3108&;#177;0．0010），P〈0．01]；[（0.3999&;#177;0．0120）,（0．3108&;#177;0．0010），P〈0．01]；[（0．3855&;#177;0．0066），（0．3108&;#177;0．0010），P〈0．01]，吗啡依赖组与盐酸纳洛酮催促戒断3h组比较差异无统计学意义[（0．3780&;#177;0．0094），（0．3855&;#177;0．0066），P〉0．05]。盐酸纳洛酮催促戒断1h组与戒断3h组肿瘤坏死因子α阳性细胞吸光度差异有显著性[（0．3999&;#177;0．0120），（0．3855&;#177;0．0066），P〈0．05]。结论：肿瘤坏死因子α参与了吗啡依赖和戒断的病理生理过程，可能是药物依赖形成中的脑损伤初始因素之一。     

Changes in adenosine receptor sensitivity in morphine-tolerant and -dependent mice

Treatment of mice with either a 75-mg morphine pellet (72 h) s.c. or 100 mg/kg of morphine s.c. (3.5 h) did not alter the ED50 of (-)-N6-(phenylisopropyl)adenosine (PIA) in the tail-flick assay. Under the same treatment conditions, caffeine became a more potent antagonist of PIA-induced analgesia, and the dose-response curve for the locomotor effects of caffeine was shifted to the left. There was no change from control in the distribution of caffeine to the brain in mice pretreated with morphine. Brain levels of PIA were decreased significantly at the two highest doses used to elicit analgesia in morphine-implanted mice when compared to control. Adenosine receptor binding assays, utilizing [3H]PIA and [3H]diethylphenylxanthine as agonist and antagonist ligands, respectively, revealed significant increases in the Bmax values for both ligands without changes in Kd in morphine-implanted mice when compared to control. These data suggest that there is an increase in sensitivity to drugs which interact with adenosine receptors in morphine-tolerant and -dependent mice.     

Potentiation of narcotic-induced antinociception by tripelennamine in morphine-tolerant and drug-naive mice

The ability of tripelennamine and chlorpheniramine to potentiate morphine- and pentazocine-induced antinociception in drug-naive and morphine-tolerant mice was tested utilizing the hot-plate method. Both tripelennamine and chlorpheniramine alone produced dose-dependent increases in hot plate latency which were naloxone reversible. Cross-tolerance developed between tripelennamine and morphine, whereas no cross-tolerance developed between chlorpheniramine and morphine. Neither tripelennamine nor chlorpheniramine significantly potentiated morphine-induced antinociception in drug-naive mice. The effects of tripelennamine and morphine were additive. Tripelennamine but not chlorpheniramine, however, significantly potentiated antinociception produced by low but not high doses of pentazocine in drug-naive mice. Furthermore, in morphine-tolerant mice, tripelennamine, but not chlorpheniramine, potentiated both morphine- and pentazocine-induced antinociception. It is concluded that the abuse of various narcotic-tripelennamine combinations can be attributed, at least in part, to a specific property of tripelennamine to potentiate narcotic effects in the drug-naive and morphine-tolerant state.     

Essential role of the synaptic vesicle protein synapsin II in formalin-induced hyperalgesia and glutamate release in the spinal cord

The synaptic vesicle protein synapsin II plays an important role in the regulation of neurotransmitter release and synaptic plasticity. Here, we investigated its involvement in the synaptic transmission of nociceptive signals in the spinal cord and the development of pain hypersensitivity. We show that synapsin II is predominantly expressed in terminals and neuronal fibers in superficial laminae of the dorsal horn (laminae I-II). Formalin injection into a mouse hindpaw normally causes an immediate and strong release of glutamate in the dorsal horn. In synapsin II deficient mice this glutamate release is almost completely missing. This is associated with reduced nociceptive behavior in the formalin test and in the zymosan-induced paw inflammation model. In addition, the formalin evoked increase in the number of c-Fos IR neurons is significantly reduced in synapsin II knockout mice. Touch perception and motor coordination, however, are normal indicating that synapsin II deficiency does not generally disrupt sensory and/or motor functions. Antisense-mediated transient knockdown of synapsin II in the spinal cord of adult animals also reduced the nociceptive behavior. As the antisense effect is independent of a potential role of synapsin II during development we suggest that the hypoalgesia in synapsin II deficient mice does involve a direct 'pain-facilitating' effect of synapsin II and is not essentially dependent on potentially occurring developmental alterations. The distinctive role of synapsin II for pain signaling probably results from its specific localization and possibly from a specific control of glutamate release.     

Genetic deletion of synapsin II reduces neuropathic pain due to reduced glutamate but increased GABA in the spinal cord dorsal horn

The synaptic vesicle protein synapsin II is specifically expressed in synaptic terminals of primary afferent nociceptive neurons and regulates transmitter release in the spinal cord dorsal horn. Here, we assessed its role in nerve injury-evoked molecular and behavioral adaptations in models of peripheral neuropathic pain using mice genetically lacking synapsin II. Deficiency of synapsin II resulted in reduced mechanical and cold allodynia in two models of peripheral neuropathic pain. This was associated with decreased glutamate release in the dorsal horn of the spinal cord upon sciatic nerve injury or capsaicin application onto the sciatic nerve and reduced calcium signals in spinal cord slices upon persistent activation of primary afferents. In addition, the expression of the vesicular glutamate transporters, VGLUT1 and VGLUT2, was strongly reduced in synapsin II knockout mice in the spinal cord. Conversely, synapsin II knockout mice showed a stronger and longer-lasting increase of GABA in lamina II of the dorsal horn after nerve injury than wild type mice. These results suggest that synapsin II is involved in the regulation of glutamate and GABA release in the spinal cord after nerve injury, and that a imbalance between glutamatergic and GABAergic synaptic transmission contributes to the manifestation of neuropathic pain.     

Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats

The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on morphine tolerance in rats. Male Wistar rats were implanted with two intrathecal (i.t.) catheters with or without a microdialysis probe, then received a continuous i.t. infusion of saline (control) or morphine (15 microg/h) and/or amitriptyline (15 microg/h) for 5 days. The results showed that amitriptyline alone did not produce an antinociceptive effect, while morphine alone induced antinociceptive tolerance and down-regulation of spinal glutamate transporters (GLAST, GLT-1, and EAAC1) in the rat spinal cord dorsal horn. Co-administration of amitriptyline with morphine attenuated morphine tolerance and up-regulated GLAST and GLT-1 expression. On day 5, morphine challenge (10 microg/10 microl) resulted in a significant increase in levels of the excitatory amino acids (EAAs), aspartate and glutamate, in CSF dialysates in morphine-tolerant rats. Amitriptyline co-infusion not only markedly suppressed this morphine-evoked EAA release, but also preserved the antinociceptive effect of acute morphine challenge at the end of infusion. Glial cells activation and increased cytokine expression (TNFalpha, IL-1beta, and IL-6) in the rat spinal cord were induced by the 5-day morphine infusion and these neuroimmune responses were also prevented by amitriptyline co-infusion. These results show that amitriptyline not only attenuates morphine tolerance, but also preserves its antinociceptive effect. The mechanisms involved may include: (a) inhibition of pro-inflammatory cytokine expression, (b) prevention of glutamate transporter down-regulation, and even up-regulation of glial GTs GLAST and GLT-1 expression, with (c) attenuation of morphine-evoked EAA release following continuous long-term morphine infusion.     

微管相关蛋白1B和突触素I在FMR1基因敲除小鼠脑组织中的表达及相关性

目的 了解FMR1基因敲除小鼠脑组织中微管相关蛋白1B的改变是否与突触的异常有关，MAP1B在脆性X综合征的发病机制中是否通过调节突触数量的改变起作用，以探讨脆性X综合征的发病机制。方法 将小鼠分为成年KO（KO6W）组、成年WT(WT6W)组、新生KO(KO1W)组、新生WT(WT1W)组4组，每组10只，用免疫组化法检测MAP1B及SYN的分布和表达。用图象分析仪分别对大脑皮质、海马及小脑DAB显色的平均光密度值（MOD）进行采集，分析不同基因型及不同年龄组MAP1B和SYN在各脑区MOD值的差异，以及二者之间的相关性。结果 KO6W组及KO1W组小鼠各个脑区中MAP1B与SYN的改变均无明显相关（p>0.05）。结论 FMR1基因敲除小鼠MAP1B与突触素Ⅰ的表达之间并无显著相关关系，提示MAP1B在脆性X综合征的发病机制中不是通过调节突触数量的改变起作用的。     

'Knock-down' of spinal CB1 receptors produces abnormal pain and elevates spinal dynorphin content in mice

Recent studies demonstrate the possible existence of tonic modulatory control of nociceptive input mediated by spinal cannabinoid receptors (CB1). Accordingly, it is predicted that a reduction in the spinal CB1 receptors may enhance sensitivity to sensory stimuli and a decrease in spinal antinociceptive potency to cannabinoid agonists. An antisense oligodeoxynucleotide (ODN) specific to the CB1 receptor was used to 'knock-down' CB1 receptors in the lumbar spinal cord and dorsal root ganglia by the local, repeated intrathecal (i.th.) administration of the ODN. This treatment resulted in a decrease in lumbar spinal CB1 receptor expression accompanied by a decrease in the response thresholds to both innocuous tactile and noxious thermal stimuli. The antinociceptive action of the CB1 agonist, WIN 55,212-2, by i.th. administration was also significantly attenuated after treatment with the antisense ODN. Similar treatment using a mismatch control ODN had no effect on receptor protein or on sensory thresholds. The effects of the antisense ODN treatment on sensory thresholds were fully reversed after discontinuation of the ODN injection. The antisense ODN treated rats also showed a significant increase in lumbar spinal dynorphin A. Acute i.th. injection of MK-801 or an antidynorphin antiserum blocked the antisense ODN-induced tactile and thermal hypersensitivity. These data support the possibility of endogenous inhibitory cannabinoid tone to limit spinal afferent input of thermal and tactile stimuli. Lifting of this inhibitory tone through a 'knock-down' of spinal CB1 receptors apparently lowers the thresholds for sensory input, as reflected by the actions of MK-801 to block tactile and thermal hypersensitivity. The increased spinal dynorphin may act to further promote afferent outflow and abnormal pain because sequestration of spinal dynorphin with antiserum also reverses the manifestations of abnormal pain following knock-down of CB1 receptors.     

实验性脓毒症小鼠白细胞基因表达谱的变化

目的　应用基因芯片技术分析脂多糖 (LPS)诱导的脓毒症小鼠白细胞基因表达谱变化。方法　 5 0只C5 7BL/6J小鼠随机分为脓毒症模型组 (n =2 5 )和正常组 (n =2 5 )。腹腔内注射LPS (15mg/kg)制备小鼠脓毒症模型 ,以肺脏、肝脏、肾脏及胰腺组织病理学变化鉴定模型。应用含 12 4 89条小鼠全长基因的寡核苷酸芯片分别检测脓毒症小鼠和正常小鼠血白细胞的基因表达谱并重复 3次 ,Ratio均数 (RatioAverage,RA) >3及RA <- 3的基因为脓毒症表达差异基因 ,分析表达差异基因与脓毒症之间的关系。结果　脓毒症差异表达基因 5 91中表达上调者为 35 4条 ,下调者为 2 5 7条。脓毒症表达显著增高基因包括 ;转录因子基因 8条、信号转导基因 12条、炎症反应基因 10条、免疫反应基因 4条、黏附分子基因 3条、急性反应蛋白基因 3条、防御反应基因 3条、蛋白酶基因 2条、细胞内吞基因 2条、细胞凋亡基因 4条、代谢酶基因 5条、运输蛋白基因 2条、血管生成基因 1条。脓毒症表达显著降低基因包括 :信号转导基因 1条、黏附分子基因 1条、细胞凋亡基因 1条、防御反应基因 2条、转录因子基因 2条、代谢酶基因 1条。结论　应用芯片技术研究脓毒症小鼠基因表达谱 ,其基因变化的机制模式可能为 :炎症信号激活TPK信号通路及G蛋白介导的