Rho激酶在失血性休克大鼠心肌收缩功能障碍中的作用

目的:观察Rho激酶对失血性休克大鼠心肌收缩力的影响。方法:利用离体乳头肌张力测定技术和心脏灌流技术,测定失血性休克后不同时间大鼠离体左室乳头肌在K-H液中的等长收缩张力的变化,以及大鼠的血流动力学指标(包括LVSP、±dp/dtm ax),并观察Rho激酶在其中的作用。结果:失血性休克后大鼠离体乳头肌收缩力和离体心脏血流动力学指标随着休克时间延长逐渐降低,在休克1 h、2 h以及4 h时乳头肌对异丙肾上腺素的收缩反应性显著低于正常对照组,同时休克后不同时点心肌组织Rho激酶活性发生明显变化,在休克1 h、2h、4 h Rho激酶活性显著低于正常对照组,Rho激酶活性变化与大鼠离体乳头肌收缩力和离体心脏血流动力学参数变化之间呈明显相关性,Rho激酶激动剂U-46619在浓度为10-8m ol/L预孵育休克2 h离体乳头肌或离体心脏后,离体乳头肌对异丙肾上腺素收缩力明显增加,最大收缩张力显著高于休克2 h组,曲线向左移。U-46619也可明显改善休克离体心脏血流动力学指标,Rho激酶特异性抑制剂Y-27632可明显拮抗由U-46619引起的休克大鼠离体乳头肌收缩反应性和离体心脏的改善作用。结论:Rho激酶在休克心肌收缩功能调节中发挥重要作用。     

抗钠钙交换体特异位点抗体对离体大鼠心脏功能和血管张力的影响及其与哇巴因、（±）Bay K8644作用的比较

 目的：比较抗钠钙交换体（NCX）特异位点（α-1重复序列124HNFTAGDLGPSTIVGSAAFNMF145）抗体、传统强心药哇巴因以及L型Ca2+通道激动剂（±）Bay K8644对离体大鼠心脏和血管功能的影响,以探求新的强心作用靶点。方法：选用成年大鼠,体重250~300 g,快速分离心脏和胸主动脉,利用Langendorff离体心脏灌流装置和血管环张力测定系统观察10 nmol/L、20 nmol/L和40 nmol/L抗NCX特异位点抗体以及哇巴因（0.5 mmol/L）、（±）Bay K8644（0.1 mmol/L）对心脏血流动力学指标左室发展压、左心室内压上升/下降最大速率（±dp/dtmax）、冠脉阻力以及胸主动脉环张力的影响。结果：10 nmol/L、20 nmol/L和40nmol/L抗NCX特异位点抗体剂量依赖性地使大鼠离体心脏左室发展压、＋dp/dtmax和－dp/dtmax增加,表明心脏收缩和舒张效率均增强。给药过程中均没有发生心律失常。哇巴因（0.5 mmol/L）和（±）Bay K8644（0.1 mmol/L）对正常离体灌流大鼠心脏左室发展压及＋dp/dtmax也有增强作用,作用强度与抗NCX特异位点抗体（40 nmol/L）的作用相当,但（±）Bay K8644（0.1 mmol/L）对－dp/dtmax无明显影响,哇巴因（0.5 mmol/L）则有使－dp/dtmax下降的趋势。哇巴因（0.5 mmol/L）在给药5 min后,多数离体心脏出现≥5 beats/min的早博,（±）Bay K8644（0.1 mmol/L）给药过程中离体大鼠心脏没有出现心律失常。结论：抗NCX特异位点抗体可以同时增强离体灌流大鼠心脏的收缩和舒张活动,并且不增加心律失常的发生率,同时对灌流心脏冠脉阻力以及离体大鼠的胸主动脉环张力也没有显著影响。     

失血性休克大鼠淋巴管低反应性的钙敏机制

目的:观察失血性休克(HS)大鼠离体淋巴管对去甲肾上腺素(NE)反应性以及钙敏感性的变化,探讨淋巴管低反应性的钙敏机制。方法:Wistar雄性大鼠随机均分为sham组(仅手术)和HS组(复制HS模型,分为休克1 h、休克2 h亚组),制备胸导管环(每组均n=48)。采用离体淋巴管张力测定技术,观察淋巴管环对NE反应性以及钙敏性[梯度Ca2+与血管紧张素Ⅱ(AngⅡ)和胰岛素(Ins)分别孵育]变化。结果:与sham组相比,HS1 h组、HS 2 h组大鼠离体淋巴管对NE反应的量效曲线以及HS 2 h组淋巴管对Ca2+的量效曲线明显右移,对NE多个浓度的反应性以及不同Ca2+浓度的收缩力、最大收缩力(Emax)、亲和力指数(pD2)均显著降低。HS大鼠离体淋巴管环与钙敏感性增强剂AngⅡ孵育后,对NE的反应性以及钙敏感性均显著升高,但仍低于sham组;与钙敏感性抑制剂Ins孵育后,对NE的反应性以及钙敏感性均显著降低。结论:HS大鼠离体淋巴管的低反应性与钙失敏有关,这是休克时淋巴管收缩性降低的机制之一。     

三七茎叶皂苷对大鼠离体工作心脏血流动力学的影响

目的:研究三七茎叶皂苷(PnGL)对离体大鼠工作心脏血流动力学指标的影响。方法:采用Langendorff离体心脏灌流方法,以左室内压(LVSP)、左室舒张末压(LVEDP)、左室发展压(LVDP)、左室内压最大上升速率(+dp/dtmax)、左室内压最大下降速率(-dp/dtmax)、心率(HR)等血流动力学参数为指标,观察PnGL灌流30min~120min对心脏血流动力学的影响。结果:中、高剂量(10mg/L、30mg/L)PnGL灌流30min~120min可使LVSP、LVDP、+dp/dtmax明显升高,同时使HR明显减慢,与空白对照组比较,差异有统计学意义(P<0.05,P<0.01)。对LVEDP及-dp/dtmax虽有改善趋势,但差异无统计学意义(P>0.05)。结论:PnGL对离体工作心脏具有正性肌力和负性频率作用。     

PKC和ROCK对硝苯地平舒张血管作用的影响

目的:探讨蛋白激酶C(PKC)及Rho相关激酶(ROCK)对硝苯地平舒张大鼠离体胸主动脉血管环作用的影响。方法:采用离体血管环灌流装置观察硝苯地平对基础状态血管环及去甲肾上腺素(NE,10~(-6)mol/L)或KCl(60mmol/L)预收缩血管环的张力变化,并利用PKC抑制剂和ROCK抑制剂等工具药观察对硝苯地平舒血管作用的影响并探讨可能机制。结果:系列浓度硝苯地平对基础状态血管环张力无明显影响,对NE和KCl预收缩的血管环具有浓度依赖性舒张作用(P 0. 05),去内皮组舒张作用与内皮完整组比较无明显差异。预孵PKC抑制剂星孢菌素(STA,10~(-8)mol/L)及激动剂佛波酯(PMA,10~(-7)mol/L)后,STA能增强硝苯地平对血管的舒张作用,而PMA能减弱硝苯地平对血管的舒张作用(P 0. 05);预孵ROCK抑制剂法舒地尔(fasudil,10~(-6)mol/L)及激动剂血管紧张素Ⅱ(Ang-Ⅱ,10-9mol/L)后,fasudil能增强硝苯地平对血管的舒张作用,而Ang-Ⅱ能减弱硝苯地平对血管的舒张作用(P 0. 05);钾通道阻滞剂BaCl_2(10~(-4)mol/L)、四乙胺(10~(-3)mol/L)、格列本脲(10~(-5)mol/L)和4-氨基吡啶(10~(-3)mol/L)对硝苯地平的舒张血管作用无明显影响。在无钙且含高浓度KCl的溶液中,硝苯地平可浓度依赖性地抑制累积浓度的CaCl_2对大鼠离体主动脉环的收缩作用(P 0. 05)。在无钙液中,硝苯地平对NE所引起的收缩无明显影响。结论:硝苯地平能够呈浓度依赖性地舒张大鼠主动脉,其舒张血管作用为非内皮依赖性,且与抑制细胞外钙内流密切相关,其舒张血管作用部分与抑制PKC和ROCK作用相关。     

内皮素(Endothelin)对大鼠心血管功能的影响

给正常大鼠静脉注射3μg/Kg内皮素,可引起动脉血压下降和心肌收缩力减弱,使LVPSP和±LV dP/dtmax呈显著而持久的降低。给利血平和阿托品化的大鼠注射同样剂量的内皮素,使血压一过性升高。用不同剂量的内皮素灌流心脏,可引起冠状动脉收缩,使灌流压升高,并有强大的抑制心功能的作用,使LVPSP和±LV dp/dt max显著降低,且具有剂效关系。在浓度为10~(-8)M时,可出现心肌挛缩和心律失常,内皮素具有强大的收缩主动脉环的作用,其ED_(50)为3×10~8M,较NE强约5倍。提示内皮素可能是在机体严重损伤(如休克、缺血、缺氧)等条件下,血管内皮细胞产生、释放或漏出的一种致病因子,参与某些疾病的发病过程。     

三七茎叶皂苷对大鼠离体工作心脏血流动力学的影响

<正>目的:研究三七茎叶皂苷(PnGL)对离体大鼠工作心脏血流动力学的影响。方法:采用Langendorff离体心脏灌流方法,以左室内压(LVSP)、左室舒张末压(LVEDP)、室内压最大上升速率(+dp/dtmax)     

ERK1/2及JNK参与DL0805抑制血管紧张素Ⅱ引起的大鼠离体胸主动脉环收缩

目的研究Rho激酶抑制剂DL0805对血管紧张素Ⅱ(AngⅡ)引起的大鼠离体胸主动脉环收缩反应的影响及其可能的机制。方法测定离体血管张力观察大鼠胸主动脉环收缩反应,Western blot检测大鼠离体胸主动脉环ERK1/2和JNK蛋白磷酸化,和AngⅡ1型受体(AT1R)蛋白表达水平。结果 DL0805(10、25和50μmol/L)浓度依赖性地抑制AngⅡ(100 nmol/L)引起的内皮完整或去内皮的大鼠离体胸主动脉环收缩(P<0.01,P<0.001),DL0805(25和50μmol/L)抑制AngⅡ(100 nmol/L)诱导的ERK1/2和JNK的活化(P<0.05,P<0.01和P<0.001),但DL0805(5、25和50μmol/L)对AngⅡ刺激的血管环AT1R蛋白表达水平无显著影响。结论 DL0805抑制AngⅡ引起的大鼠离体胸主动脉环收缩,其机制可能与其抑制AngⅡ诱导的ERK1/2和JNK活化有关。     

Cl-通道活动对自发性高血压大鼠血管张力的影响

目的：观察自发性高血压大鼠(SHR)血管平滑肌细胞Ca2+激活Cl-通道［ICl（Ca）］的活动。 方法： 测定离体肠系膜血管床灌注压和离体尾动脉肌条血管张力, 以其对去甲肾上腺素(NE)收缩反应的变化作为舒缩活动的指标。 结果： （1）SHR肠系膜动脉和尾动脉对NE收缩反应显著大于Wistar大鼠。（2）硝呋咪酸可显著抑制NE诱发的肠系膜动脉和尾动脉收缩反应，并具有浓度依赖性，SHR肠系膜动脉和尾动脉收缩活动受硝呋咪酸的抑制程度明显小于Wistar大鼠。（3）SHR肠系膜动脉对低氯缓冲液的反应显著大于Wistar大鼠。 结论： SHR肠系膜动脉和尾动脉血管平滑肌的Ca2+激活Cl-通道的活动增强，并导致血管对NE的反应性增高。这可能是在高血压的发生过程中引起和维持较高血管张力和外周血流阻力的因素之一。     

长期去窦弓神经大鼠胸主动脉收缩和舒张功能的改变

目的:观察长期去窦弓神经(SAD)对大鼠胸主动脉收缩和舒张功能的影响。方法:10周龄SD大鼠行SAD术或假手术(Sham),用离体动脉环实验测定SAD术后4、8、16、32周和相应Sham组大鼠胸主动脉对去甲肾上腺素(NE)和氯化乙酰胆碱(ACh)的收缩和舒张反应。结果:SAD大鼠离体胸主动脉环对NE的收缩反应进行性强于Sham组,对ACh的舒张反应进行性弱于Sham组。结论:大鼠去窦弓神经后单纯血压不稳定可引起类似于实验性高血压动物模型的血管功能的改变。     

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