胃肠道伤害性刺激诱导中缝背核触液神经元Fos表达

本文以ＣＢ－ＨＲＰ逆行追踪和原癌基因ｃ－ｆｏｓ表达技术相结合,观察胃肠道伤害性刺激后中缝背核触液神经元Ｆｏｓ的表达。在中缝背核发现三种标记神经元,包括ＣＢ－ＨＲＰ逆行标记神经元（３０８）、Ｆｏｓ阳性神经元（４２）和ＣＢ－ＨＲＰ／Ｆｏｓ双重标记神经元（５）。本研究提示中缝背核含有一些具有双重功能的神经元,它们既在脑－脑脊液神经体液回路中传递信息,又在胃肠道伤害性刺激的中枢传递和功能调控中起一定的作用     

Fos Expression in the Rat Brain After Intraperitoneal Injection of Staphylococcus Enterotoxin B and the Effect of Vagotomy

The current study was designed to locate the neuronal activation in rat brain following intraperitoneal injection of Staphylococcus enterotoxin B (SEB) and observe the consequence of preliminary subdiaphragmatic vagotomy on SEB-induced brain Fos expression to clarify the role of the vagus nerve in sensation and transmission of abdominal SEB stimulation. The results showed that intraperitoneal SEB (1 mg/kg) induced a robust Fos expression in widespread brain areas. A significant increase of Fos immunoreactive cells were observed in the solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus, ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid nucleus, ventromedial part of thalamus, dorsomedial part of thalamus, hypothalamic paraventricular nucleus, lateral habenula, and lateral septum nucleus following SEB challenge. In hypothalamic paraventricular nucleus, in addition to the dense Fos expression in the parvocellular portion, some Fos-positive cells were also observed in the anterior magnocellular nucleus of the complex. Double immunofluorescence studies showed that these Fos-immunoreactive cells were mostly oxytocinergic. The results also showed that subdiaphragmatic vagotomy largely attenuated, but not totally abrogated, the brain Fos expression induced by abdominal administration of SEB. Our data suggest that peripheral SEB stimulation can induce activation of neurons in widespread brain areas and that the vagus plays a crucial role in transmitting the signal of abdominal immune stimulation to the brain.     

NADPH-d and Fos reactivity in the rat spinal cord following experimental spinal cord injury and embryonic neural stem cell transplantation

AimsThe aim of this study is to determine the role of nitric oxide (NO) in neuropathic pain and the effect of embryonic neural stem cell (ENSC) transplantation on NO content in rat spinal cord neurons following spinal cord injury (SCI).Main methodsNinety adult male Sprague–Dawley rats were divided into 3 groups (n = 30, each): control (laminectomy), SCI (hemisection at T12–T13 segments) and SCI + ENSC. Each group was further divided into sub-groups (n = 5 each) based on the treatment substance (L-NAME, 75 mg/kg/i.p.; l-arginine, 225 mg/kg/i.p.; physiological saline, SF) and duration (2 h for acute and 28 days for chronic groups). Pain was assessed by tail flick and Randall–Selitto tests. Fos immunohistochemistry and NADPH-d histochemistry were performed in segments 2 cm rostral and caudal to SCI.Key findingsTail-flick latency time increased in both acute and chronic L-NAME groups and increased in acute and decreased in chronic l-arginine groups. The number of Fos (+) neurons decreased in acute and chronic L-NAME and decreased in acute l-arginine groups. Following ENSC, Fos (+) neurons did not change in acute L-NAME but decreased in the chronic L-NAME groups, and decreased in both acute and chronic l-arginine groups. NADPH-d (+) neurons decreased in acute L-NAME and increased in l-arginine groups with and without ENSC transplantation.SignificanceThis study confirms the role of NO in neuropathic pain and shows an improvement following ENSC transplantation in the acute phase, observed as a decrease in Fos(+) and NADPH-d (+) neurons in spinal cord segments rostral and caudal to injury.     

大鼠面部伤害性刺激后纹状体边缘区内原癌基因c-fos和NOS的表达

为了研究纹状体边缘区和痛觉的关系,用c-fos和NADPH－d双标记方法研究了大鼠面部伤害性刺激后c-fos蛋白（Fos）和NOS在纹状体边缘区的表达。面部伤害性刺激后30分钟,边缘区中即出现Fos表达,刺激后3小时,Fos表达达最高峰,而且主要在边缘区部位表达。正常大鼠纹状体边缘区中有密集的NOS阳性神经元及纤维,面部伤害性刺激3小时后,纹状体其余部位的NOS阳性胞体及纤维减少或消失,但边缘区中仍保留,并可见少数Fos和NOS双标记细胞,提示纹状体边缘区可能和面部痛觉的调制有关。     

Changes in the levels of activity of spinal neurons after long-lasting vibrational stimulation of the shin muscles in rats

Vibrational stimulation of the tendon of the mm.gastrocnemius+soleus (100 sec^–1) in rats anesthetized with chloral hydrate (400 mg/kg) resulted in the appearance of considerable Fos immunoreactivity in the lumbar spinal cord (L1-L6), as compared with that in intact animals. Total densities of Fos-immunopositive (Fos-ip) neurons in each of the examined segments were higher than 40 units per 40-μm-thick slice; the respective index reached the maximum at the L4 level (78.9 ± 2.3 cells). Most Fos-ip neurons were localized in laminae 4 to 7 of the gray matter, both ipsi- and contralaterally with respect to the side of stimulation (28.5 ± 0.6 and 28.4 ± 0.6, respectively). Single Fos-ip motoneurons were found bilaterally in the ventral horn motor nuclei. Thus, activation of muscle spindle receptors induced by vibrational stimulation applied to the Achilles tendon induces noticeable bilateral c-fos expression in spinal neuronal networks related to transmission of proprioceptive muscle-born impulsation.     

Activation of AMP-activated protein kinase stimulates Na+,K+-ATPase activity in skeletal muscle cells

Contraction stimulates Na(+),K(+)-ATPase and AMP-activated protein kinase (AMPK) activity in skeletal muscle. Whether AMPK activation affects Na(+),K(+)-ATPase activity in skeletal muscle remains to be determined. Short term stimulation of rat L6 myotubes with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), activates AMPK and promotes translocation of the Na(+),K(+)-ATPase α(1)-subunit to the plasma membrane and increases Na(+),K(+)-ATPase activity as assessed by ouabain-sensitive (86)Rb(+) uptake. Cyanide-induced artificial anoxia, as well as a direct AMPK activator (A-769662) also increase AMPK phosphorylation and Na(+),K(+)-ATPase activity. Thus, different stimuli that target AMPK concomitantly increase Na(+),K(+)-ATPase activity. The effect of AICAR on Na(+),K(+)-ATPase in L6 myotubes was attenuated by Compound C, an AMPK inhibitor, as well as siRNA-mediated AMPK silencing. The effects of AICAR on Na(+),K(+)-ATPase were completely abolished in cultured primary mouse muscle cells lacking AMPK α-subunits. AMPK stimulation leads to Na(+),K(+)-ATPase α(1)-subunit dephosphorylation at Ser(18), which may prevent endocytosis of the sodium pump. AICAR stimulation leads to methylation and dephosphorylation of the catalytic subunit of the protein phosphatase (PP) 2A in L6 myotubes. Moreover, AICAR-triggered dephosphorylation of the Na(+),K(+)-ATPase was prevented in L6 myotubes deficient in PP2A-specific protein phosphatase methylesterase-1 (PME-1), indicating a role for the PP2A·PME-1 complex in AMPK-mediated regulation of Na(+),K(+)-ATPase. Thus contrary to the common paradigm, we report AMPK-dependent activation of an energy-consuming ion pumping process. This activation may be a potential mechanism by which exercise and metabolic stress activate the sodium pump in skeletal muscle.     

Moderately Different NADPH-Diaphorase Positivity in the Selected Peripheral Nerves after Ischemia/ Reperfusion Injury of the Spinal Cord in Rabbit

1. To vicariously investigate the nitric oxide synthase (NOS) production after spinal cord injury, NADPH-d histochemistry was performed on the selected peripheral nerves of adult rabbits 7 days after ischemia. The effect of transient spinal cord ischemia (15 min) on possible degenerative changes in the motor and mixed peripheral nerves of Chinchilla rabbits was evaluated.2. The NADPH-diaphorase histochemistry was used to determine NADPH-diaphorase activity after ischemia/reperfusion injury in radial nerve and mediane nerve isolated from the fore-limb and femoral nerve, saphenous nerve and sciatic nerve separated from the hind-limb of rabbits. The qualitative analysis of the optical density of NADPH-diaphorase in selected peripheral nerves demonstrated different frequency of staining intensity (attained by UTHSCSA Image Tool 2 analysis for each determined nerve).3. On the seventh postsurgery day, the ischemic spinal cord injury resulted in an extensive increase of NADPH-d positivity in isolated nerves. The transient ischemia caused neurological disorders related to the neurological injury—a partial paraplegia. The sciatic, femoral, and saphenous nerves of paraplegic animals presented the noticeable increase of NADPH-d activity. The mean of NADPH-diaphorase intensity staining per unit area ranged from 134.87 (±32.81) pixels to 141.65 (±35.06) pixels (using a 256-unit gray scale where 0 denotes black, 256 denotes white) depending on the determined nerve as the consequence of spinal cord ischemia. The obtained data were compared to the mean values of staining intensity in the same nerves in the limbs of control animals (163.69 (±25.66) pixels/unit area in the femoral nerve, 173.00 (±32.93) pixels/unit area in saphenous nerve, 186.01 (±29.65) pixels/unit area in sciatic nerve). Based on the statistical analysis of the data (two-way unpaired Mann–Whitney test), a significant increase (p≤0.05) of NADPH-d activity in femoral and saphenous nerve, and also in sciatic nerve (p≤0.001) has been found. On the other hand, there was no significant difference between the histochemically stained nerves of fore-limbs after ischemia/reperfusion injury and the same histochemically stained nerves of fore-limbs in control animals.4. The neurodegenerative changes of the hind-limbs, characterized by damage of their motor function exhibiting a partial paraplegia after 15 min spinal cord ischemia and subsequent 7 days of reperfusions resulted in the different sensitivity of peripheral nerves to transient ischemia. Finally, we suppose that activation of NOS indirectly demonstrable through the NADPH-d study may contribute to the explanation of neurodegenerative processes and the production of nitric oxide could be involved in the pathophysiology of spinal cord injury by transient ischemia.     

Induction of glycerol phosphate dehydrogenase gene expression during seizure and analgesia

Using mRNA differential display, we found that the gene for NAD(+)-dependent glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) is induced in rat brain following seizure activity. Northern blot and in situ hybridization analysis confirmed the differential display results; they also showed, in a separate model of neuronal activation, that after thermal noxious stimulation of the hind-paws, a similar increase in GPDH mRNA occurs in the areas of somatotopic projection in the lumbar spinal cord. Surprisingly, administration of analgesic doses of morphine or the nonsteroidal antiinflammatory drugs aspirin, metamizol (dipyrone), and indomethacin also increased GPDH mRNA levels in rat spinal cord. The opioid receptor antagonist naloxone completely blocked morphine induction of GPDH but had no effect on GPDH induction by noxious heat stimulation or metamizol treatment, implicating different mechanisms of GPDH induction. Nevertheless, in all cases, induction of the GPDH gene requires adrenal steroids and new protein synthesis, as the induction was blocked in adrenalectomized rats and by cycloheximide treatment, respectively. Our results suggest that the induction of the GPDH gene upon peripheral noxious stimulation is related to the endogenous response to pain as it is mimicked by exogenously applied analgesic drugs.     

Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after cyclophosphamide (CYP)-induced bladder inflammation. In urethan-anesthetized Wistar rats with cystitis, intravesical saline distension significantly (P 相似文献   

Topography of Fos-Immunoreactive and NADPH-d-Reactive Neurons in the Limbic Structures of the Basal Forebrain and in the Hypothalamus during Realization of Motivated Operant Movements in Rats

We estimated in rats the expression of early gene c-fos (marker of neuronal activation) and NADPH-diaphorase activity (NO-synthase marker) in the limbic structures of the basal forebrain and in the hypothalamus. Estimations were performed in the norm, in the state of starvation, and after realization of long-lasting (repeated 4 to 12 times per minute for 30 min) motivated stereotyped food-procuring forelimb movements. In food-deprived animals, a significantly greater (Р < 0.05), as compared with the control, number of Fos-immunoreactive (Fos-ir) and NADPH-diaphorase-reactive (NADPH-dr) neurons was observed in limbic structures, namely in the medial septum (MS), nuclei of the vertical and horizontal branches of the diagonal fascia (VDB and НDB), magnocellular preoptic nucleus (MCPO), complex of the substantia innominata−basal nucleus of Meynert of the pallidum, SI-GP(B), as well as in the laterodorsal tegmental nucleus (LDTg), medial part of the pallidum (MGP), paraventricular and lateral nuclei of the hypothalamus (Pa and LH), and islands of Calleja (ICj and ICjM). In the limbic structures and pontine nuclei of rats of the experimental group (that performed operant movements), greater mean densities of labeled neurons were found in the succession LDTg < SI < MCPO < GP(B) < MS < VDB < HDB. The maximum mean density of Fos-ir neurons (13.8 ± 0.9 labeled nuclei within 200 × 200 μm² area) was found in the HDB. In the hypothalamic nuclei of starving rats, c-fos expression was two times higher than that in the control. After realization of operant movements, the intensity of expression in the LH was somewhat smaller, while in the Ра it was higher. The maximum density of NADPH-dr neurons was observed in the Pa (303.4 ± 18.7 cells), in the ICj and ICjM (287 ± 11.6 and 260 ± 8.7 neurons, respectively), and in the MGP (93 ± 6.7 labeled cells). When analyzing the distribution of labeled neurons in experimental rats, we found high densities of double-labeled cells (Fos + NADPH-d positivity) in the Pa, MGP, ICj, and ICjM. Such specificity of changes in the c-fos expression and NADPH-d reactivity in the hypothalamus correlates, perhaps, with the formation of motivation signals related to a delay in food accessibility and supply of food. Modifications of neuronal activity in limbic structures reflect involvement of the latter in the formation of motor programs for food-procuring movements and their realization. Neirofiziologiya/Neurophysiology, Vol. 41, No. 1, pp. 32–40, January–February, 2009.     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

Somatosensory afferent inputs release 5-HT and NA from the spinal cord

Endogenous serotonin (5-HT) and noradrenaline (NA) release by somatosensory afferent inputs was investigated at the level of the spinal cord using in vivo microdialysis technique combined with high performance liquid chromatography and electrochemical detection (HPLC-ECD). Selective stimulation of large myelinated Aβ afferent fibers significantly increased 5-HT release to 151.1 ±10.1% of the control, but did not affect NA release. However, selective stimulation of small myelinated Aδ fibers released NA rather than 5-HT. The NA level enhanced to 128.8±6.4% of the control after Aδ fibers were stimulated with the intensity of 6 times threshold. Stimulation of unmyelinated C fibers unavoidably excited the Aβ and Aδ afferent fibers, causing both 5-HT and NA release from the spinal cord. The results suggest that both innocuous and noxious information may activate serotonergic descending pathways. The noradrenergic descending pathways are only triggered by noxious inputs transmitted by small afferent fibers.     

Rat plasmacytoid dendritic cells are an abundant subset of MHC class II+ CD4+CD11b-OX62- and type I IFN-producing cells that exhibit selective expression of Toll-like receptors 7 and 9 and strong responsiveness to CpG

We have identified in the rat a new subset of MHC class II(+) CD4(+)CD3(-)CD11b(-) leukocytes that produce high amounts of type I IFN upon viral stimulation and that appeared homologous to plasmacytoid DC (pDC) previously described in humans and mice. These cells exhibited the following phenotype: CD5(+),CD90(+),CD45R(+),CD45RC(+),CD11c(-),CD161a(+),CD200(+),CD172a(+),CD32(+),CD86(+). Rat pDC did not express the DC-specific marker OX62 and were more abundant in the spleen than the classical CD4(+) and CD4(-) subsets of OX62(+)CD11b(+) DC we previously described that produced very little, if any, type I IFN. Spleen pDC exhibited an undifferentiated morphology and rapidly died in vitro, but showed extensive dendrite formation, survival, maturation, and moderate type I IFN production upon stimulation by oligonucleotides containing type B CpG motifs (CpG ODN). Type A CpG ODN and CD40 ligand induced pDC to produce large amounts of type I IFN, but did not promote maturation. CpG ODN and CD40 ligand, but not influenza virus, induced IL-12p40 and IL-6 secretion. Spleen pDC did not produce IL-12p70, TNF-alpha, IL-1beta, or IL-10 using these stimulation conditions. Correlating with their strong responsiveness to virus and CpG ODN, rat pDC specifically expressed Toll-like receptor 7 and 9 mRNA. Fresh spleen pDC were poor stimulators of allogenic CD4(+) and CD8(+) T cells, but became potent inducers of allogenic T cell proliferation as well as Th1 differentiation after stimulation by type B CpG. Therefore, rat pDC appear very similar to human pDC, indicating that the specific phenotype and functions of pDC have been highly conserved between species.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。     

Direct hypertonic stimulation of the rat supraoptic nucleus increases c-fos expressionin glial cells rather than magnocellular neurones

We investigated whether hypertonicity acts directly on supraoptic neurones to activate c-fos expression. Hypertonic artificial cerebrospinal fluid was infused into the supraoptic nucleus (SON) via a microdialysis probe implanted 24 h previously. The rats were decapitated after 90 min for immunohistochemistry with a Fos protein antibody. Direct hypertonic stimulation increased Fos protein expression in glial cells, identified by glial fibrillary acidic protein immunoreactivity, but not in magnocellular neurones. Similarly, with in situ hybridisation c-fos mRNA expression was predominantly seen in glial cells. Fos expression in SON neurones was stimulated by systemic hypertonicity even with a microdialysis probe in the SON, and magnocellular neurones expressed Fos after direct microinjection of cholecystokinin-8S into the SON. Thus, while direct hypertonic stimulation of SON neurones activates secretion of vasopressin and oxytocin, the c-fos gene is not activated, unlike following systemic hypertonic stimulation. This indicates that excitation of neuronal electrical and secretory activity does not necessarily lead to activation of the c-fos gene. Activation of c-fos expression in glial cells by direct hypertonic stimulation may reflect their role in regulating brain extracellular fluid composition. Received: 11 March 1996 / Accepted: 24 July 1996     

大鼠三叉神经脊束间质核接受内脏和躯体伤害性信息的calbindin D-28k神经元向臂旁核的投射

应用荧光金（FG）逆行束路追踪结合Fos和calbindin D-28k(CB)免疫荧光组织化学三重标记法,观察了大鼠三叉神经脊束间质核（INV）接受口面部皮肤和上消化道伤害性信息的CB神经元向臂旁核（PB）的投射。结果显示,口周刺激组FG逆标细胞和Fos免疫反应阳性细胞主要分布于注射和刺激同侧INV的背侧边缘旁核（PaMd）和三叉旁核（PaV）;大量的CB免疫阳性细胞分布于双侧INV。同侧INV内FG逆标细胞中有77.3%呈CB免疫反应阳性,40.7%呈Fos免疫反应阳性。在FG和CB双标记的神经元中,又有一部分（约38.5%）为FG／CB／Fos三标细胞。上消化道刺激组的FG逆标细胞、CB免疫阳性细胞和FG／CB双标细胞的数量和分布与口周刺激组相似,但Fos免疫阳性细胞分布于双侧的INV。在同侧INV,FG／Fos双标细胞占FG逆标细胞总数的41.9%,FG／CB／Fos三标细胞占FG／CB双标细胞的52.0%。以上结果提示,INV直接投射到PB的CB神经元接受口面部皮肤和上消化道的伤害性信息,CB神经元可能参与经INV中继的外周伤害性信息向PB的传递。     

大鼠延髓至下丘脑腹内侧核的儿茶酚胺能投射神经元在胃伤害性刺激后的Fos表达

本实验用ＨＲＰ注入下丘脑腹内侧核结合逆行追踪与抗ＦＯＳ蛋白和抗酪氨酸羟化酶（ＴＨ）抗血清双重免疫细胞化学相结合的三重标记方法,对大鼠孤束核和延髓腹外侧区至下丘脑腹内侧核的儿茶酚胺能投射神经元在胃伤害性刺激后的ｃ－ｆｏｓ表达进行了观察。本文发现孤束核和延髓腹外侧区有七种不同的标记细胞：ＨＲＰ、Ｆｏｓ、ＴＨ单标细胞Ｆｏｓ／ＨＲＰ、Ｆｏｓ／ＴＨ、ＨＲＰ／ＴＨ双标细胞和Ｆｏｓ／ＨＲＰ／ＴＨ三标细胞。上述七种标记细胞主要分布在延髓中段和尾段孤束核的内侧亚核和延髓腹外侧区以及两者之间的网状结构。ＨＲＰ标记细胞以注射侧为主,对侧有少量分布。本文结果证明,大鼠孤束核、延髓腹外侧区和网状结构内儿茶酚胺能神经元有些至下丘脑腹内侧核的投射,其中一部分儿茶酚胺能神经元参与了胃伤害性刺激的传导和调控。     

Kinetic attributes of rat liver microsomal adenosine 5' triphosphate phosphohydrolase (ATPase)

The kinetic properties of the rat liver microsomal ATPase, with respect to Na(+), K(+) and AT P requirements were examined. Presence of Na(+) and K(+), or both hardly caused any stimulation of the enzyme activity. The Km values for Na(+) and K(+) were substantially low (0.32 and 0.05 mM, respectively), compared to those reported for the Na(+), K(+) ATPasesfrom different tissues. Substrate kinetics studies revealed that in the absence of Na(+) and K(+), ATP is an activator of the enzyme. The enzyme displayed increased activity with increase in the energy of activation in the absence of Na(+) and K(+). The activity was partially inhibited by ouabain only in the presence of Na(+) and K(+). The results suggest that the liver microsomal enzyme is not a Na(+), K(+) ATPase, but has requirement of monovalent cations for the regulation of its activity. Also, the beta3 subunit of the enzyme has a Km lowering effect.     

两种非甾体类抗炎药对清醒状态血管源性头痛模型大鼠颅内Fos表达的影响

目的通过观察血管源性头痛清醒动物模型中Fos阳性细胞在三叉神经节及三叉神经脊束核尾侧亚核的分布情况,明确两种非甾体类抗炎药NSAID对乙酰氨基酚及布洛芬在头痛控制中,在颅内特定区域的作用机理。方法 30只雄性SD大鼠随机分为对照组(生理盐水组)、对乙酰氨基酚组、布洛芬组,每组给药后50 min分别给予频率为20 Hz、电流为3~5 mA和脉宽为0.25 ms的电刺激,刺激后给予大鼠灌注固定取脑,分别在颅内取三叉神经节及三叉神经脊束核尾侧亚核制作石蜡切片,进行免疫组织化学染色,利用Image J软件对阳性细胞进行计数统计。结果电刺激后盐水组与非甾体类药物组在双侧三叉神经节、三叉神经脊束核尾侧亚核Fos蛋白表达的差异具有显著统计学意义,对乙酰氨基酚组与布洛芬组在双侧三叉神经节、三叉神经脊束核尾侧亚核Fos蛋白表达未见统计学差异。结论给予非甾体类抗炎前后在双侧三叉神经节、三叉神经脊束核尾侧亚核的Fos表达的改变提示三叉神经节、三叉神经脊束核尾侧亚核参与了疼痛的传递和表达以及药物对疼痛控制的药理过程。