增龄进程淋巴细胞NF-κB信号通路胞外配体mRNA差异表达特征及淫羊藿总黄酮的干预效应

目的：研究衰老进程淋巴细胞NF-κB信号通路胞外配体相关分子mRNA差异表达特征及淫羊藿总黄酮（EF）的干预效应。方法：采用NF-κB信号通路寡核苷酸基因芯片，选取SD大鼠在衰老进程中的几个特定年龄：3天（3d），4月龄（4m），10月龄（10m），18月龄（18m），27月龄（27m），研究衰老进程中淋巴细胞NF-κB信号通路中上游相关分子功能类——胞外配体mRNA水平的整体表达特征及差异，并观察EF对老年大鼠（27m）该类分子的干预效应。结果：随着增龄，大鼠淋巴细胞NF-κB信号通路胞外配体mRNA平均表达降低，一般在3d和4m表达较低，在10m达峰值，而后逐渐降低。EF干预之后，老年组的上述基因mRNA变化可至少提高到10-18m水平。结论：衰老进程中，淋巴细胞NF-κB信号通路胞外配体mRNA表达随增龄而降低，而EF可显著提高老年组上述分子mRNA变化。     

淫羊藿总黄酮(EF)对老龄大鼠Th1、Th2、Th3细胞的调节作用

目的：探讨淫羊藿总黄酮（EF）对衰老大鼠脾淋巴细胞Th1、Th2、Th3各类细胞因子的调节作用.方法：采用流式细胞仪,监测比较老龄大鼠脾脏淋巴细胞凋亡率;采用Th1、Th2、Th3 cDNA芯片,分别检测正常青年组（YC）、老龄大鼠组（OM）、EF组、NF-KB阻断剂组（PDTC）、PDTC＋EF组的Th1、Th2、Th3,各类细胞因子信号差异表达.结果：①老龄大鼠普遍存在淋巴细胞过度凋亡现象,EF可显著抑制这种过度凋亡状态.②YC组,Th1、Th2、Th3类细胞因子之间处于平衡状态（P＞0.05）;OM组Th1、Th2、Th3类细胞因子表达比YC组增高,呈Th2、Th3类细胞因子优势应答（P＜0.05）.③EF组Th1、Th2、Th3类细胞因子均较OM组明显降低（P＜0.05）,其趋势与YC组近似,并且Th1、Th2、Th3类细胞恢复平衡.④NFKB通路抑制后（PDTC组）,Th1、Th2、Th3类细胞因子平衡失调,Th2优势更加明显（P＜0.05）;而PDTC＋EF组,Th1、Th2、Th3各组表达值则较PDTC组下调,其组内Th1和Th2也重新达到一种相对平衡状态.结论：老龄大鼠脾淋巴细胞过度凋亡,Th1、Th2、Th3类细胞因子分泌增高,Th2、Th3类细胞因子优势应答;EF可以抑制淋巴细胞过度凋亡,校正老龄大鼠Th1、Th2、Th3类细胞因子之间的比例失衡,重塑Th1-Th2-Th3细胞免疫调节网络的良性平衡.     

大鼠松果体细胞增龄变化

目的:探讨大鼠松果体细胞增龄变化。方法:SD大鼠,随机分为1～2月龄组,4～5月龄组,11～12月龄组和≥24月龄组4个组。采用H-F染色、Benda胶质细胞染色和TUNEL法细胞凋亡染色光镜观察,超薄切片透射电镜观察。结果:松果体细胞数从4～5月龄组至≥24月龄组递减(P<0.001),而胶质细胞数随增龄递增(P<0.01),松果体细胞凋亡随增龄增多(P<0.01),松果体细胞胞质随增龄电子密度降低,细胞器减少,线粒体扩张、嵴断裂呈空泡状,粗面内质网排列紊乱、池扩张,脂滴增多。结论:大鼠松果体随增龄而出现松果体细胞减少、胶质细胞增多,松果体细胞退变。这些变化可能是导致机体衰老的原因之一。     

EF延缓HPAT轴衰老的基因表达谱研究

目的：淫羊藿总黄酮(EF)延缓下丘脑-垂体-肾上腺-胸腺(HPAT)轴衰老的分子机制。方法：利用基因芯片技术，分别检测淫羊藿总黄酮组、右归饮组、桃红四物汤组、老年大鼠对照组及青年大鼠对照组下丘脑、垂体、肾上腺、脾脏淋巴细胞的基因表达谱。结果：老年大鼠和青年大鼠相比，HPAT轴多种神经递质、激素、细胞因子或其受体表达下调；EF组HPAT轴多种神经递质、激素、细胞因子或其受体表达上调；右归饮组及桃红四物汤组未见广泛的调节作用。结论：老年大鼠HPAT轴与生长、发育、衰老相关的基因表达以衰退的表现为主；EF能上调神经递质受体的表达并通过NEI网络的下行通路激活神经内分泌和免疫系统；通过下调促凋亡、抗增殖基因，上调抗凋亡、促增殖基因的表达，重塑淋巴细胞基因表达的平衡，延缓免疫衰老。     

补肾活血液延缓雄性大鼠增龄性骨质疏松的研究

目的：评价补肾活血液延缓雄性大鼠骨衰老的作用。方法：40只SD雄性大鼠随机分为4组,每组10只,分别为24月龄本底对照组、27月龄增龄对照组、补肾活血液低剂量组和补肾活血液高剂量组,增龄对照组不做任何处理,低剂量组、高剂量组均自24月龄给药至27月龄。进行相应处理后分别测定各组大鼠全身骨矿物密度（GBMD）、右侧股骨抗弯强度（FBS）和血清骨钙素（BGP）、尿羟脯氨酸（U-Hyp）与肌苷（U-Cr）。结果：补肾活血液高剂量组的GBMD及FBS均高于27月龄增龄对照组和补肾活血液低剂量组,但低于24月龄本底对照组;高剂量组的BGP明显高于增龄对照组（P<0.05）,U-Hyp/Cr明显低于增龄对照组（P<0.05）,都与本底对照组相接近;低剂量组的BGP低于本底对照组（P<0.05）,U-Hyp/Cr明显高于本底对照组（P<0.05）,都与增龄对照组相接近。结论：补肾活血液具有剂量依赖性地降低全身BMD的增龄性减少率和股骨抗弯强度的增龄性降低率,而延缓雄性大鼠增龄性骨质疏松的作用。     

EF调控老年大鼠淋巴细胞基因表达谱中凋亡相关信号分子表达的研究

目的：揭示EF对老年大鼠淋巴细胞凋亡相关信号分子及通路的调节机制。方法：利用基因芯片技术，并比较老年大鼠、青年大鼠、EF干预后的淋巴细胞基因表达。结果：老年大鼠与青年大鼠比较，促进细胞凋亡作用的基因表达显著上调，具有抗凋亡作用的基因表达显著下调；具有抗增殖作用的基因表达显著上调，具有促进细胞增殖作用的基因表达显著下调；参与淋巴细胞活化增殖及免疫反应等基本信号通路的组成元件中，多个重要信号分子的表达显著下调。EF组抗淋巴细胞凋亡的几个上游因子如CD28、TGFβ及c-Jun、c-Fos、c-Myc等癌基因显著上调；促细胞凋亡基因Caspasel、Caspase2、Caspase3、Caspase6、CalpainⅡ、Cathepsins、Dnaseγ、PKCdelta等表达显著下调；Cathepsin B、Mtal、NF-kappa B、Notch等抗凋亡基因表达显著上调。显著上调促细胞增殖基因PCNA、A-raf、CyclinG-associated kinase等的转录，显著下调抗增殖的Rb等基因的转录。显著上调免疫细胞效应及功能的基本调节因子CD2、CD3、CD5、TCR、IL-2、IL-2R(CD25)、CD28、CTLA4的表达。结论：EF能上调老年大鼠淋巴细胞抗凋亡基因表达的同时，下调抗增殖基因的表达；上调促增殖基因表达的同时，下调抗增殖基因的表达，重塑基因表达良性平衡；还协同调节TCR／CD3、CD28、CTLA4、TGFβ、IL-2R等介导的信号转导通路，发挥抗凋亡效应。     

胸腺细胞凋亡在EAE模型中的变化

目的研究EAE大鼠胸腺细胞凋亡的变化规律,为探讨胸腺在EAE发病中的作用提供理论依据。方法应用光镜、电镜观察正常组、EAE发病第3天组、恢复期组大鼠胸腺细胞变化情况,应用caspase-3免疫组化染色及流式细胞术观察比较胸腺细胞凋亡情况。结果电镜、光镜观察显示正常组和恢复期组胸腺结构基本一致,皮质髓质分界清楚,淋巴细胞密集,核呈蓝紫色,发病第3天组胸腺明显萎缩,皮质变薄,淋巴细胞数减少,并可见凋亡淋巴细胞;caspase-3免疫组化染色显示发病第3天组胸腺皮质凋亡淋巴细胞数目明显增多;流式细胞术显示发病第3天组大鼠胸腺细胞凋亡率显著升高(P<0.05),恢复期组凋亡率与正常组相比无统计学意义(P>0.05)。结论 EAE大鼠发病后第3天胸腺细胞明显减少并发生凋亡,随病情恢复淋巴细胞增加、凋亡细胞减少,表明胸腺具有自我恢复能力,其变化与EAE形成有关。     

孕激素对更年期雌性大鼠脾细胞凋亡及相关基因的调控作用

为了解孕激素对更年期雌性大鼠脾细胞凋亡及相关基因的调控作用。首先通过应用Annexin V-FITC/PI双染色流式细胞仪测定脾细胞凋亡率;通过RT-PCR检测脾细胞凋亡基因Bcl-2、Bax的表达;RIA法测血孕酮(P)水平。结果发现更年期组血孕激素水平明显低于青年组和孕激素组(P<0.01),孕激素组与青年组相比差别无显著意义(P>0.05);更年期组大鼠脾细胞凋亡率高于青年组(10.3%和7.7%,P<0.05),促凋亡基因Bax的转录水平也高于青年组;孕激素组脾细胞的凋亡率与更年期组比较无显著差异,孕激素组促凋亡的Bax基因转录水平高于更年期组大鼠(P<0.01),而Bcl-2基因未见显著差异。研究结果提示,衰老过程中脾淋巴细胞凋亡增加,并受到相关基因的调控,孕激素治疗未能逆转更年期雌性大鼠脾细胞凋亡的增加,且使更年期大鼠脾细胞促凋亡的Bax基因表达上调。     

NF-κB介导促红细胞生成素神经细胞保护作用的研究

目的：观察促红细胞生成素（EPO）对谷氨酸（Glu）诱导的大脑皮质神经元损伤的保护作用和核因子-κB（NF-κB）介导的细胞内信号转导机制。方法：采用1日龄Wistar大鼠皮层神经细胞体外原代培养技术,建立Glu兴奋性毒性神经细胞损伤模型。实验分为正常对照组、Glu组、EPO组和吡咯烷二硫氨基甲酸（PDTC,NF-κB活化阻断剂）组。倒置显微镜下观察细胞的形态学改变;MTT法测定细胞存活率;流式细胞术测定细胞凋亡率评价细胞损伤程度。结果：Glu处理后神经细胞形态明显受损,EPO组神经细胞形态趋于正常,PDTC组细胞形态与Glu组相似;与正常对照组相比,Glu组神经细胞存活率明显下降、凋亡率明显升高,差异均有统计学意义（P〈0.01）;而与Glu组相比,EPO组神经细胞存活率明显增高下降、凋亡率明显下降,差异均有统计学意义（P〈0.01）。与EPO组相比,PDTC组细胞存活率明显下降、凋亡率明显升高,差异均有统计学意义（P〈0.01）,这些变化与Glu组相似。结论：EPO对Glu诱导的大脑皮质神经元损伤的具有保护作用,其胞内信号转导机制涉及到NF-κB的活化。     

大鼠生精小管体视学及PCNA、凋亡表达的发育变化研究

目的　探讨大鼠生精小管面积、管腔等体视学参数与生精细胞增殖、凋亡在发育过程中的变化及其之间的关系。　方法　应用免疫细胞化学、凋亡细胞原位检测和图像分析技术。　结果　大鼠从出生后生精小管平均面积逐渐增加 ,于生后 3月龄时达到最大 ,除与生后 6月龄组差异不显著外 ,与其他各组间差异显著 (P <0 0 5 ) ,6月龄后生精小管面积逐渐减少 ,2 5月龄时生精小管面积与 3周龄时相当 ;生精小管在 3周龄时开始出现管腔 ,在生后 6月龄时其平均面积最大 ,与其他各组间差异显著或极显著 (P <0 0 5或P <0 0 1) ,至生后 2 5月龄 ,管腔不明显 ,多被结缔组织填充 ;生精细胞间于生后 10月龄开始出现空泡 ,生后 2 5月龄空泡化明显 ,生精小管基膜及间质血管增生严重。PCNA及凋亡的阳性表达在生后 3周龄出现高峰 ,生后 2 5月龄细胞凋亡又出现 1个高峰。　结论　 1 生后 3周龄至 3月龄生精细胞增殖旺盛是生精小管平均面积迅速增大的原因之一。 2 生后一定阶段生精小管管腔的出现与生精细胞的凋亡有关 ,而生精小管管腔的出现有利于精子的生成与运输。 3 衰老大鼠生殖功能的下降与其组织结构的纤维化及生精小管基膜厚度增加等因素有关     

Topical organization of the projections of neurons of the substantia nigra and the ventral field of the tegmentum of the midbrain to the head of the caudate nucleus of the cat

Neuroscience and Behavioral Physiology -     

Asymmetry of the internal connections of the striate cortex of the cat in the projection zone of the center of the field of vision

Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field. Laboratory of Visual Physiology and Laboratory of Central Nervous System Morphology, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 12, pp. 23–29, December, 1996.     

Characteristics of the topographic interrelation of the head of the pancreas and the duodenum and pathology of the organs of the pancreatoduodenal area

Seventy pancreatoduodenal complexes of 55 patients with chronic pancreatitis and tumours of this zone and 15 patients died from other diseases are studies histotopographically . The pieces of the pancreatic head tissue in the medial wall of the duodenum were found in 12 cases of the first group and in 4 control cases. The pancreatic tissue consisted either of all elements of this organ or cystically dilated ducts and seemed to infiltrate different layers of the duodenum wall. Three variants of the pancreatic head structure are suggested on the basis of anatomo-topographical interrelationships of the pancreatic head and duodenum. In 12 out of 14 cases chronic pancreatitis and carcinoma of organs of this zone were combined with the variants of the pancreatic head structure, in 2 cases there was a true heterotopy . Pathogenetic significance of these variants for the development of chronic pancreatitis is discussed.     

Influence of the level of the transmembrane potential on the dynamics of the extinction of the amplitude of the synaptic reactions of the snail under voltage clamping conditions

The influence of the level of the transmembrane potential on the dynamics of the extinction of the amplitudes of summary excitatory postsynaptic currents arising in identified giant parietal neurons in response to rhythmic stimulation of the intestinal nerve was investigated in a preparation of the isolated CNS of the common snail in order to identify the possibility of the participation of the postsynaptic element in synaptic plasticity. It was demonstrated that, at a greater value of the transmembrane potential, the decrease in the amplitudes of the postsynaptic currents which have been induced by rhythmic stimulation takes place more rapidly. It was also demonstrated that at a higher frequency of stimulation of the nerve, the effect of the influence of the membrane potential level on the dynamics of the synaptic reactions is more prominent. The data obtained may be regarded as an argument in favor of the possibility of the participation of the post-synapse in plasticity. This study was partially supported by the Russian Basic Research Fund (project No. 94-04-12209). Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 1, pp. 171–179, January–February, 1995.     

Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.     

Effect of the conditions of adaptation of the optic analyzer to the function of the thermoreceptors of the human skin

Summary A discussion is presented of the effect produced by light stimulation applied to the optic analyzer alone on the function of the temperature analyzer. The cutaneous-temperature analyzer was kept on constant illumination and temperature. The light effects from the retinal photoreceptors on the cutaneous thermoceptor system led to reflex changes of the functional rate of the latter. Conditions of the optic analyzer of light adaptation caused reflex adjustment of cold receptors as to heating. Dark adaptation of the eyes changed the functional state of the cold receptors, corresponding to their adjustment to low temperatures.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 3, pp. 3–6, March, 1964