右美托咪啶对罗哌卡因致惊厥后小鼠负性情绪的影响

目的:探讨不同剂量右美托咪啶预处理对罗哌卡因致惊厥后小鼠负性情绪和中央杏仁核外侧囊状部(CeC)内磷酸化细胞外信号调节激酶(phosphorylated-extracellular signal-regulated kinase,p-ERK)表达的影响。方法:各组小鼠分别腹腔注射2.4、4.8和9.6μg/kg右美托咪啶10 min后,腹腔注射半数致惊厥剂量罗哌卡因,离线视频记录各组小鼠给药后30 min内惊厥发生率及惊厥潜伏期和持续时间;旷场、高架十字迷宫试验观察各组小鼠惊厥发生24 h后的负性情绪变化;免疫组织化学染色和Western Blot检测各组小鼠CeC内p-ERK的表达情况。结果:右美托咪啶预处理可剂量依赖性地降低罗哌卡因致小鼠惊厥的发生率、延长惊厥潜伏期、并缩短惊厥持续时间;增加惊厥发生24 h后小鼠旷场中央区域活动时间百分比、高架十字迷宫开臂停留时间百分比和开臂进入次数百分比;减少CeC内p-ERK表达。结论:右美托咪啶预处理可以剂量依赖性地改善罗哌卡因致惊厥后小鼠的负性情绪,可能与抑制CeC内ERK磷酸化增加有关。     

鞘内给予氯胺酮通过抑制星形胶质细胞内STAT3的磷酸化改善大鼠神经病理性痛的研究

目的:观察神经病理性痛大鼠鞘内给予氯胺酮对于脊髓背角星形胶质细胞内信号转导和转录活化因子3(STAT3)磷酸化水平的影响。方法:采用L5脊神经结扎(SNL)方法制作慢性神经病理性痛模型,利用机械刺激法和热板法连续观察造模后大鼠的痛行为变化;应用免疫组织化学染色和Western Blot方法观察大鼠腰膨大节段胶质纤维酸性蛋白(GFAP)和磷酸化STAT3(pSTAT3)的表达水平。结果:SNL模型大鼠机械性痛阈和热痛阈均明显降低,且术后一周内均保持在较低的水平(P0.01),从术后第3 d起鞘内连续给予氯胺酮至第7 d能够明显缓解大鼠患侧后爪的机械性痛敏和热痛敏。免疫荧光组织化学染色显示:pSTAT3在星形胶质细胞上有表达,且SNL后pSTAT3与GFAP在脊髓背角的表达均升高。Western Blot结果显示:与对照组相比,SNL后第7 d脊髓背角的pSTAT3的表达明显上调(P0.05),从术后第3 d鞘内连续给予氯胺酮至第7 d能够明显下调STAT3的磷酸化水平。结论:鞘内给予氯胺酮能够明显下调脊髓背角星形胶质细胞内STAT3的磷酸化水平从而达到缓解疼痛的目的。     

雷公藤内酯醇(T10)通过抑制脊髓背角内p38-MAPK的磷酸化发挥镇痛作用的机制研究

目的:观察鞘内给予雷公藤内酯(triptolide,T10)对于慢性炎性痛和神经病理性痛模型大鼠脊髓背角小胶质细胞内p38丝裂原激活的蛋白激酶(p38 mitogen-activated protein kinase,MAPK)的磷酸化水平的影响。方法:采用大鼠足底注射完全弗式佐剂(complete Freund’s adjuvant,CFA)构建慢性炎性痛模型,L5脊神经结扎(spinal nerve ligation,SNL)和坐骨神经分支选择性结扎(spared nerve injury,SNI)的方法制作慢性神经病理性痛模型。利用von Frey丝刺激法连续观察造模后大鼠的痛行为变化;应用免疫荧光染色方法观察大鼠腰膨大节段胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和电离钙绑定衔接分子1(ionized calcium binding adaptor molecule-1,Iba-1)的表达水平;应用Western Blot方法观察大鼠腰膨大节段p38 MAPK的磷酸化水平。结果:(1)行为学结果显示:CFA、SNL、SNI模型大鼠机械性痛阈均明显降低,且术后一周内与正常对照组相比均保持在较低水平(P0.01)。从术后第1 d起鞘内连续给予T10至第7 d,分别观察到T10能够明显提高上述模型大鼠手术侧后足的机械性痛阈(P0.05);但T10在SNL模型和SNI模型大鼠中的效果要弱于CFA引起的慢性炎性痛(P0.05)。(2)免疫荧光染色结果显示:CFA、SNL和SNI模型大鼠腰膨大脊髓背角内GFAP、Iba-1的表达明显高于正常对照组,而p-p38 MAPK阳性产物主要表达于小胶质细胞内。(3)Western Blot结果显示:造模后7 d脊髓背角内p-p38 MAPK的表达明显上调,鞘内给予T10后可以显著下调脊髓背角内p38的磷酸化水平(P0.05)。结论:鞘内给予T10有效缓解由于CFA、SNL和SNI诱导的慢性痛模型大鼠的机械性痛阈的机制可能是通过下调脊髓背角内p38 MAPK信号通路的磷酸化水平,进而达到抑制小胶质细胞和星形胶质细胞的活化。其次,T10对不同类型的疼痛模型的作用效果存在差异,对由CFA引起的慢性炎性痛的作用效果要强于由SNL和SNI诱导的慢性神经病理性痛。     

c-fos反义寡核苷酸探针对大鼠炎性痛和神经病理性痛的影响

研究c-fos反义寡核苷酸探针(antisense oligodeoxynucleotides,ASO)对大鼠炎性痛和神经病理性痛的作用效果,为临床慢性疼痛的治疗提供理论依据。以大鼠足底注射福尔马林(formalin)致炎性痛模型和腰5脊神经结扎(spinal nerve ligation,SNL)诱导神经病理性痛模型为基础,分别观察鞘内给予c-fosASO对两种模型大鼠的行为学及腰5脊髓背角Fos阳性神经元表达的影响。行为学检测结果表明:和正义探针(SO)组以及生理盐水(NS)对照组相比,鞘内预先给予c-fosASO后,大鼠足底注射福尔马林引起自发缩足反射次数和SNL诱导的机械性缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL)均有明显缓解(P<0.05),而c-fosASO不能逆转SNL诱导的神经病理性痛。免疫荧光组织化学染色结果发现:和对照组相比,鞘内给予c-fosASO能显著抑制福尔马林和SNL诱导的大鼠腰髓背角Fos阳性神经元的增加。上述结果提示,脊髓背角c-fos的活化对于炎性痛和神经病理性痛的发展都有显著意义,而抑制其活化在预防阶段比治疗阶段对慢性疼痛的缓解作用更为显著。     

曲古抑菌素A通过抑制脊髓背角内的炎症反应减轻大鼠神经病理性痛

目的:观察曲古抑菌素A (TSA)对脊神经结扎(SNL)大鼠镇痛效果及分子机制。方法:40只健康雄性Sprague Dawley(SD)大鼠随机分为假手术组(sham)、曲古抑菌素A处理组(TSA)、脊神经结扎组(SNL)和SNL+TSA组(SNL+TSA)。采用L5脊神经结扎(SNL)的方法建立神经病理性痛模型,鞘内注射TSA进行干预,通过von Frey丝和热板实验检测大鼠的痛敏,应用免疫荧光染色方法观察大鼠脊髓背角内HDAC1的表达情况;应用Western Blot方法观察大鼠脊髓背角内胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白分子1(Iba-1)的表达水平;应用real time RT-PCR方法检测大鼠脊髓背角内TNF-α、IL-1β和IL-6的mRNA表达水平。结果:SNL模型大鼠术后机械性痛阈值和热痛阈值均显著降低(P 0.05),鞘内给予TSA能够明显缓解大鼠患侧后足机械性痛敏和热痛敏; SNL模型大鼠脊髓背角内HDAC1的表达较对照组明显增加,而鞘内注射TSA可显著抑制其表达; SNL术后脊髓背角内GFAP和Iba-1的表达显著升高(P 0.05),鞘内给予TSA能够明显下调GFAP和Iba-1的表达; SNL术后大鼠脊髓背角内TNF-α、IL-1β和IL-6的表达较对照组明显上调(P 0.05),而鞘内给予TSA能够显著逆转这一趋势。结论:鞘内给予TSA能够通过抑制脊髓HDAC1表达缓解大鼠神经病理性痛。     

抑制AQP4降低大鼠脊神经节ERK表达,减轻坐骨神经结扎导致神经病理性疼痛

目的探讨AQP4抑制剂对坐骨神经结扎导致的神经病理性疼痛的作用及其可能机制。方法制作大鼠坐骨神经慢性压迫性损伤(CCI)模型,采用热痛刺激仪测量热痛感受性潜伏期,Western blot和免疫荧光(双重染色)方法检测ERK, JNK, p38表达。结果神经损伤可诱导ERK, JNK, p38信号分子表达及卫星胶质细胞活化,AQP4抑制剂TGN-020则削弱ERK,JNK和p38信号分子及卫星胶质细胞的活化;p-ERK和GFAP共表达的细胞在损伤后明显增多,TGN-020则显著降低这一表达。结论抑制AQP4减轻坐骨神经结扎导致的神经病理性疼痛与抑制神经节卫星胶质细胞活化和MAPK信号通路活化相关。     

脊髓刺激术对神经病理性痛模型大鼠脊髓背角内NR2B受体和星形胶质细胞激活的影响

目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对L5脊神经结扎(spinal nerve ligation,SNL)诱导的神经病理性痛(neuropathic pain,NP)大鼠脊髓背角内NMDA受体亚单位NR2B的表达和星形胶质细胞激活的影响。方法:成年雄性SD大鼠48只,随机分为4组:正常组(不做任何处理);SCS组(植入SCS装置并给予SCS刺激);SNL+sham SCS组(给予SNL手术并植入SCS装置,但不进行刺激);SNL+SCS组(SNL手术并给予SCS刺激)。SCS刺激是在SNL术后第6～10 d进行(8 h/d),第10 d刺激结束后处死动物。运用行为学方法检测慢性痛状态下大鼠后肢对机械性刺激的反应阈值;采用免疫组织化学染色和Western blot方法分别检测脊髓背角内NR2B和星形胶质细胞的标志物GFAP的表达变化。结果:(1)SNL术后大鼠手术侧后足机械性痛敏显著增加,第6～10 d给予SCS刺激后,可观察到大鼠的痛行为学表现有明显缓解;(2)免疫组化结果显示:与SNL+sham SCS组相比,SNL+SCS组大鼠脊髓背角内NR2B和GFAP免疫阳性细胞的数量显著减少;(3)Western blot结果显示:给予SCS刺激后,SNL大鼠腰膨大段脊髓背角内NR2B的表达量显著下调,同时GFAP的表达量也明显有所降低。结论:给予SCS刺激可以有效地缓解SNL模型大鼠的神经病理性痛的行为学表现;该作用可能与SCS刺激抑制脊髓背角内NR2B的表达和星形胶质细胞的激活密切相关。     

神经病理性痛条件下前额叶皮质内代谢型谷氨酸受体第5亚型的表达及分布变化

目的:观察慢性神经病理性痛状态下内侧前额叶皮质(medial prefrontal cortex,mPFC)内代谢型谷氨酸受体第5亚型(metabotropic glutamate receptor 5,mGluR5)表达与疼痛及其伴随情绪反应之间的关系。方法:采用雄性SD(Sprague Dawley)大鼠40只,随机分为5组(正常组和手术后1、3、5、7 d组)。应用免疫荧光组织化学染色、Western Blot和行为学方法,观察腰5脊神经结扎(L5 spinal nerve ligation,SNL)术后1、3、5、7 d大鼠的情绪反应和mPFC内mGluR5的表达情况。结果:大鼠神经病理痛模型制作成功后,其50%机械性缩足阈值(paw withdrawal threshold,PWT)显著下降,且伴有焦虑样行为。免疫荧光组织化学染色结果显示:术后7 d大鼠mPFC内mGluR5在细胞内的分布发生改变,与正常组大鼠相比,mGluR5被募集到细胞突起中。Western Blot结果显示:术后7 d,mPFC内mGluR5的表达量减少,与正常对照组相比,有统计学差异(P0.05)。结论:慢性神经病理性痛伴随焦虑样症状可导致大鼠mPFC内mGluR5的表达减少,分布发生改变。     

水通道蛋白4在大鼠坐骨神经损伤导致的神经病理性疼痛中的作用及机制

目的 :对坐骨神经损伤大鼠的脊髓后角神经元中水通道蛋白4(AQP4)和细胞外调节蛋白激酶(ERK)信号通路的激活之间的关联性做系统的探讨。方法 :制作大鼠坐骨神经慢性压迫性损伤(CCI)模型,经腹腔给予AQP4抑制剂TGN-020,应用DMSO组作对照,应用Von Frey纤毛进行机械痛检测,以免疫荧光(双重染色)检测脊髓ERK、NeuN的表达。结果 :脊髓后角p-ERK和NeuN共定位的细胞在神经损伤后可见增加,而给予TGN-020后,同时表达p-ERK和NeuN的细胞明显减少。TGN-020抑制AQP4的表达可以减轻神经损伤产生的痛觉敏感性异常。结论 :抑制AQP4可以通过抑制脊髓后角神经元中ERK通路的活化来改善坐骨神经损伤导致的神经病理性疼痛。     

神经病理性痛大鼠海马CA1区锥体神经元树突及树突棘的变化

目的:观察神经病理性痛条件下大鼠海马CA1区锥体神经元树突形态和树突棘密度的变化。方法:建立大鼠腰5脊神经结扎(L5 spinal nerve ligation,SNL)神经病理性痛模型,对照组为假手术组即只暴露腰5脊神经,不结扎。利用Von Frey纤维丝检测其50%机械性缩足阈值(paw withdrawal threshold,PWT),判断SNL模型是否成功。通过高尔基(Golgi)染色的方法观察SNL模型后14 d海马CA1区锥体神经元树突形态和树突棘密度的变化。结果:SNL模型组大鼠CA1区锥体神经元树突棘密度升高,与对照组相比有统计学差异(P0.05),而锥体神经元树突分支数无明显差异。结论:神经病理性痛会导致海马CA1区锥体神经元树突棘密度升高。     

Role of the hormonal status of the father in involution of the thymus in the progeny

This study was aimed at assessing the consequences of the influence of exogenous androgens on the epididymal sperm of fathers for their progeny. A single injection of testosterone or dihydrotestosterone to adult rats caused a transient increase of the level of the corresponding androgen, later leading to augmentation of the androgen-dependent organs and loss of thymus weight. Hyperandrogeny and earlier age-associated involution of the thymus were observed in the male progeny of androgenized males of reproductive age. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 562–564, May, 1996     

Role of noradrenalin in the dorsal hippocampus in the mechanism of the self-stimulation response in rats

Laboratory of Neurophysiology of Reinforcement, A. I. Karaev Institute of Physiology, Academy of Sciences of the Azerbaijan SSR, Baku. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 1, pp. 5–6, January, 1990.     

Changes in the structure of the cilia of the ciliated epithelium of the bronchi in Kartagener's syndrome in children

Biopsies of bronchial mucous membrane taken from 4 children with Kartagener's syndrome and 10 children with chronic pneumonia were examined electron microscopically. Structural changes in cilia and apical parts of cells are detected in all patients with Kartagener's syndrome. Cilial changes provoked by chronic inflammatory process are shown. The importance of ultrastructural investigations of bronchial mucous membrane cilia in the understanding of pathogenesis of chronic lung conditions in children is underlined.     

The Beauty of the Network in the Brain and the Origin of the Mind in the Control of Behavior

Behavior is not adequately described as a stimulus-response process. It is initiated by the animal and is generated because of its expected outcome in the future. The outcome can be good or bad for the animal. The brain is in charge of the selection process. This is the basic function of the brain. Taking Drosophila as a study case, this paper discusses initiating activity, several examples of outcome expectations, trying out (the internal search for a suitable behavior), chaining of actions, and the functional roles of chance in action selection. It takes mental processes and states such as goals, intentions, feelings, memories, cognition, and attention as higher levels of behavioral control that have their origin in biological evolution.     

Challenges in the Management of Asthma in the Elderly

Recent literature has emphasized the clinical and socio-epidemiological significance of asthma in the elderly. However, why the disease burden remains high in this group is unclear. Elderly subjects usually have multiple chronic illnesses, and the role played by comorbidities in the context of asthma has been underappreciated. This review aims to summarize the literature associations between comorbidities and asthma in elderly patients. In addition, we discuss patient management issues.     

Role of the time interval in the effect of neurochemical signals in the changes in the ultrastructure of cortical synapses

Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 4, pp. 836–838, July–August, 1991.     

Role of the inferior colliculus in the inhibition of acoustic startle in the rat

Fifteen rats were tested for amplitude reduction of the acoustic startle response using auditory and visual prestimuli. Eight subjects then received large lesions of the inferior colliculus, and the remaining subjects served as normal controls. All animals were reassessed on a post-test identical to the pre-test. In addition, all subjects were tested for latency reduction of startle using auditory prestimuli. There were no significant differences between groups on the pre-test for startle amplitude, visual amplitude reduction, or auditory amplitude reduction, nor did the control group differ significantly on these measures from pre-test to post-test. After surgery, the lesion group displayed a large, significant increase in startle amplitude. Auditory prestimuli were no longer effective in reducing startle amplitude in this group, but visual prestimuli still produced reliable amplitude reduction. Both groups displayed reliable latency reduction to auditory prestimuli; the groups were not significantly different from each other on this measure. These data support the proposition that the inferior colliculus is part of a neural circuit for startle amplitude reduction by auditory prestimuli.