镇痛灵对雄性1型糖尿病大鼠性功能的影响

目的 :本实验以成年雄性大鼠为研究对象 ,观察和探讨中药镇痛灵对糖尿病大鼠性功能的影响。　方法 :3～ 5月龄雄性Wistar大鼠 32只 ,随机分为糖尿病组 2 2只 ,正常对照组 10只。 72h后 ,将造模成功的糖尿病大鼠随机分为 2组 :未治疗组 ;镇痛灵治疗组。第 5周测血糖 ,阿朴吗啡勃起实验后 ,乙醚麻醉下断头取血 ,分离血清 ,取一侧睾丸组织制成匀浆液 ,测定血清及组织匀浆中NO及NOS水平。　结果 :糖尿病大鼠与正常对照组比较 ,血清NO、NOS明显降低 ,差异有高度显著性 (P <0 .0 0 1) ;镇痛灵治疗组血清NO、NOS值与未治疗组比较明显升高 ,差异有显著性 (P <0 .0 1) ;阿朴吗啡勃起实验证实 ,镇痛灵治疗组大鼠阴茎勃起次数明显多于未治疗组 ,差异有显著性(P <0 .0 1) ,而与正常对照组比较 ,差异无显著性 (P >0 .0 5 )。　结论 :复方中药合剂镇痛灵有降血糖作用 ,对糖尿病并发的性功能障碍有一定治疗作用。     

肝脏缺血再灌注损伤大鼠嘌呤核苷磷酸酶活性的研究

目的:探讨大鼠肝脏低温保存及常温缺血再灌注过程中,不同保存液中嘌呤核苷磷酸酶(PNP)活性的变化.方法:将大鼠肝脏在3种不同保存液中低温保存不同时限后,用37℃Krebs-Henseleit液连续循环灌注90min,分别于不同灌注时间检测灌洗液中PNP活性的变化.结果:经过8 h的低温保存,再灌注90min后,HTK保存的肝脏中PNP明显高于UW和Celsior;经过16 h的低温保存后,再灌注60min前,HTK保存的肝脏中PNP明显高于UW和Celsior;60min后HTK和Celsior保存的肝脏中PNP明显高于UW;经过24 h的低温保存后,再灌注15min后,HTK保存的肝脏中PNP明显高于Celsior,而Celsior又明显高于UW.结论:随着低温保存和再灌注时间的延长,大鼠肝脏中PNP逐渐增高且UW液的保存效果明显优于HTK和Celsior     

缺氧诱导因子-1α在去势前后大鼠腹叶前列腺中表达的变化

目的探讨与缺氧相关的缺氧诱导因子-1α(HIF-1α)是否参与去势后前列腺萎缩过程.方法24只SD大鼠分为3组,其中A组(n=8)为假手术对照组,B组(n=8)为去势组,C组(n=8)为雄激素替代组(去势后肌注十一酸睾酮50mg/kg);术后3天处死,通过半定量RT-PCR检测与HIF-1α在去势前后前列腺表达变化.结果去势后大鼠前列腺的体积萎缩变小;雄激素替代组出现前列腺增生变大;对照组正常的大鼠前列腺有HIF-1 α mRNA低水平表达,去势组HIF-1α mRNA表达量增加,雄激素替代组HIF-1αmRNA表达量减少,与正常对照组比较,去势组的HIF-1α mRNA的表达量显著增加(P＜0.05),雄激素替代组的HIF-1αmRNA的表达量显著减少(P＜0.01).结论前列腺组织的缺氧参与去势后大鼠前列腺的早期萎缩过程.     

Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.     

核因子kB在大鼠胃缺血再灌注损伤中的表达及意义

目的研究核因子kB（NF-kB）在大鼠胃缺血再灌注损伤中的表达及意义。方法采用大鼠胃缺血再灌注（gustric ischemia/reperfusion, CI／R）模型（夹闭腹腔动脉30min后再灌注），分别于再灌注0．5、1、3、24h取胃，计算胃黏膜损伤指数。应用免疫组化、Western blot方法检测胃黏膜NF-kB p65。结果大鼠GUR后引起胃黏膜损伤，再灌注1h时损伤最明显，随后降低，24h接近正常。GI／R后胃黏膜NF—kB阳性细胞数和蛋白表达量增多，与胃黏膜损伤变化规律一致。结论NF-kB在大鼠CI／R损伤过程中发挥着重要作用。     

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor

The neurosteroid allopregnanolone (ALLO) or 3α-OH-5α-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3β position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3β-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3β-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3β-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3β-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3β-steroids can act as positive GABA_A receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3β-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.     

DSP-4, a noradrenergic neurotoxin, produces more severe biochemical and functional deficits in aged than young rats

The present study examines the effects of noradrenergic lesions (either DSP-4 i.p. or 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle on biochemical (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and choline acetyltransferase (ChAT) activity) and cortical EEG (quantitative EEG (qEEG) and high-voltage spindle (HVS) activity in young and aged rats. Near complete 6-OHDA NA lesions, but not partial DSP-4 NA lesions, increased HVS activity in young rats. DSP-4 and 6-OHDA lesions produced no significant changes in the 5-HT or DA levels or in the ChAT activity in young rats. In some of the aged rats, DSP-4 produced similar biochemical and HVS effects, as it induced in young rats. In the remainder of the aged rats, NA levels were greatly and 5-HT levels slightly decreased. DA levels and ChAT activity were unaltered in either set of aged rats. HVS activity was increased only in that group of aged rats with the greatly lowered NA content. These results suggest that: (1) some of the aged rats are more sensitive to DSP-4 treatment than young adult rats; and (2) NA depletions have to be complete to produce an increase in HVS activity in young and aged rats.     

Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D₁ and D₂ dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O₂. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [¹²⁵I]TISCH and [1251]IBZM for the D₁ and D₂ dopamine receptors, respectively. Using [¹²⁵I]TISCH, we observed no modifications of D₁ receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [¹²⁵I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D₂ dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D₂ receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages. Correspondence to: D. Guilloteau     

REPAIR AND RECOVERY FOLLOWING SPINAL CORD INJURY IN A NEONATAL MARSUPIAL (MONODELPHIS DOMESTICA)

1. Repair and recovery following spinal cord injury (complete spinal cord crush) has been studied in vitro in neonatal opossum (Monodelphis domestica), fetal rat and in vivo in neonatal opossum. 2. Crush injury of the cultured spinal cord of isolated entire central nervous system (CNS) of neonatal opossum (P4–10) or fetal rats (E15–E16) was followed by profuse growth of fibres and recovery of conduction of impulses through the crush. Previous studies of injured immature mammalian spinal cord have described fibre growth occurring only around the lesion, unless implanted with fetal CNS. 3. The period during which successful growth occurred in response to a crush is developmentally regulated. No such growth was obtained after P12 in spinal cords crushed in vitro at the level of C7–8. 4. In vivo, in the neonatal (P4–8) marsupial opossum, growth of fibres through, and restoration of, impulse conduction across the crush was apparent 1–2 weeks after injury. With longer periods of time after crushing a considerable degree of normal locomotor function developed. 5. By the time the operated animals reached adulthood, the morphological structure of the spinal cord, both in the region of the crush and on either side of the site of the lesion, appeared grossly normal. 6. The results are discussed in relation to the eventual longterm possibility of devising effective treatments for patients with spinal cord injuries.