液质联用技术联合网络药理学探讨白鲜皮治疗湿疹的作用机制＊

目的 采用液质联用技术分析白鲜皮中的主要化学成分；基于网络药理学技术研究白鲜皮治疗皮肤湿疹的活性成分、作用靶点及作用机制。方法 利用液质联用技术（LC-MS）对白鲜皮主要成分进行分析，通过质谱数据结合文献资料，对各主要成分进行快速识别；通过利用SwissADME数据库对白鲜皮潜在活性成分进行预测，筛选主要作用靶点。进行KEGG通路富集分析，最终得到白鲜皮成分-靶点-疾病-通路网络图。采用分子对接技术对主要成分和作用靶点进行验证。结果 从白鲜皮中共分析鉴定了12种成分，进一步筛选得到4种潜在活性成分，可作用于48个关键靶点和14条主要通路。结论 采用LC-MS技术结合网络药理学方法，可以快速分析白鲜皮的潜在活性成分，并初步揭示了成分-靶点-通路之间的关系。通过分子对接技术可以做作用靶点进行验证。     

五加科五加属植物的研究进展

五加科五加属植物为重要的药用植物,具有较高的药用价值,近年来越来越受到广泛关注。综述了五加属植物资源分布、生物学特性、化学成分和药理活性的研究进展。化学成分主要有挥发油、萜类、木脂素等,其中三萜包括羽扇豆烷(Lupane)型、3,4-seco-羽扇豆烷型、齐墩果烷(Oleanane)型的3β-Hydroxy齐墩果烷型和3α-Hydroxy齐墩果烷型;药理作用包括抗炎、抗应激、抗心律失常、抗血小板聚集、对免疫系统的影响、对物质代谢的影响等,以期为今后对该属植物进一步研究和开发利用提供参考。     

刺五加水提物对人精子体外运动活力的影响

目的研究刺五加水提物对正常男性精子体外运动活力的影响，探讨其可能的作用机制。方法将20例正常男性的精子通过上游优化法处理后，一组精子加入10 mg·mL^-1的刺五加水提物，另一组加入等量的Ham’s F10培养液作对照。应用计算机辅助的精子分析系统，分别测定孵育0.5，1，2，3，4，5 h后人精子各运动参数。结果随着时间的延长，加入Ham’s F10培养液的精子活动能力有不同程度的下降；加入10 mg·mL^-1的刺五加水提物后，不同时段精子的运动能力均较对照组明显提高，精子存活率、前向运动精子百分率、曲线运动速度、直线运动速度和平均路径速度与对照组比较，均明显改善(均P＜0.05)。 结论刺五加水提物能明显提高正常男性精子的体外存活率和运动能力。     

Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

Multiple tachykinin binding sites in peripheral tissues and in brain

Tachykinin binding sites in guinea pig urinary bladder (GPUB), rat salivary gland (RSG), hamster urinary bladder (HUB), rat vas deferens (RVD) and rat cerebral cortex (RCC) were compared using ¹²⁵I-Bolton Hunter conjugates of substance P (¹²⁵I-BHSP), eledoisin (¹²⁵I-BHE) and neurokinin A (¹²⁵I-BHNKA). In typical SP-P tissues (GPUB, RSG) and in RCC, SP was the most potent displacer of ¹²⁵I-BHSP and [Glp⁶, D-Pro⁹]-SP(6–11) was 90 times less active than [Glp⁶, L-Pro⁹]-SP(6–11) while SP methyl ester (SPOMe) was 5–10 times more active than the Bolton Hunter conjugate of SPOMe (I-BHSPOMe). On the other hand, in typical SP-E tissues (HUB, RVD), neurokinin A was most potent in displacing ¹²⁵I-BHE and [Glp⁶,D-Pro⁹]-SP(6–11) was over 300 times more active than [Glp⁶,L-Pro⁹]-SP(6–11) while SPOMe was 160 times less active than I-BHSPOMe. In rat cerebral cortex, the rank order of potency of tachykinins and related analogues in displacing ¹²⁵I-BHE was distinct from that of peripheral SP-E sites, with neurokinin B being the most potent displacer, and SPOMe was over 1 000 times more active than I-BHSPOMe; ¹²⁵I-BHE binding sites in CNS may represent a third category of tachykinin receptor, designated SP-N.     

Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABA_A and GABA_B mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.     

Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex.

The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy.     

Wistar大鼠运动皮层代表区的微刺激测定

在１５例氯胺酮麻醉的Ｗｉｓｔａｒ大鼠利用皮层内微刺激技术测定了躯体的运动皮层代表区。电刺激为３５０Ｈｚ的阴极串脉冲，电流最大值限为８０μＡ。结果表明大多数皮层点诱发对侧肌肉反应。虽然代表区的大小有很大个体差异，分区的相对位置是恒定的。但在分区内部未见分域排列。部分大鼠存在前部前肢区，但无一例发现前部后肢区。比较文献结果提示Ｗｉｓｔａｒ大鼠的运动皮层的分化程度比Ｌｏｎｇ－Ｅｖａｎｓ黑顶鼠低。     

Thalamocortical projections activated by phrenic nerve afferents in the cat

This study identified thalamocortical projections activated by respiratory afferents. Cortical evoked potentials were recorded in the right primary somatosensory cortex of the cat following electrical stimulation of the left C5 root of the phrenic nerve. The majority of primary sites were located in the vicinity of the postcruciate dimple, in area 3a near the 3a/3b border, corresponding to the trunk region of the cortical body map. Retrograde fluorescent tracers injected at the sites of primary activation produced labeled cells in the oralis nucleus of the ventroposterior complex [4]. Control injections made in adjacent cortical areas not activated by phrenic stimulation resulted in labeling in the ventroposterior complex which did not overlap that seen with injections of primary activation sites. We conclude that respiratory muscle afferents in the phrenic nerve elicit activity in the trunk region of primary somatosensory cortex via specific thalamocortical projections originating in the oralis portion of the thalamic ventroposterior complex.     

Chronic Ethanol Inhibits Inositol Metabolism in Specific Brain Regions

Many neurotransmitters and hormones in the nervous system transmit signals through receptors coupled to the poly-phosphoinositide (PI) signaling pathway. In this study, an in vivo protocol with (³H]inositol was used to examine the effect of chronic ethanol administration on inositol metabolism and poly-PI turnover in the cerebral cortex, hippocampus, and cerebellum of mouse brain. C57BL/6 mice were given a nutritionally complete liquid diet containing either ethanol (5%, w/v) or isocaloric sucrose for 2 months. Mice were injected intracerebrally with ^rH]inositol; after 16 or 24 hr, they were injected intraperitoneally with lithium (8 mEq/kg body weight) to inhibit the inositol monophosphatase (IP₁) activity. All mice were decapitated 4 hr after lithium injection. Labeled inositol phospholipids accounted for 16 to 23% of total labeled inositol in different regions of control mouse brain, and the percentages in the hippocampus were consistently higher than the cerebral cortex and cerebellum. In control mice, the percentages of labeled IP, after a 4-hr lithium treatment were 11.5%, 9.9%, and 3.7% for cerebral cortex, hippocampus, and cerebellum, respectively. Chronic ethanol feeding resulted in a significant (p < 0.05) decrease in the percent of labeled IP₁ and inositol phospholipids, and this effect was observed in the cerebral cortex and, to a lesser extent, hippocampus but not cerebellum. When ratios of labeled IP₁ were expressed against labeled inositol phospholipids as an index of the poly-PI turnover activity, significant decreases in IP/lipid ratios were observed in the cerebral cortex, but not the hippocampus or cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would have experienced an 8-hr period of ethanol withdrawal, compared with the 16 + 4-hr group, no differences in IP/lipid ratios were observed between the two time groups. These results illustrate regional differences in the effect of chronic ethanol on inositol metabolism in the brain, but no difference in poly-PI turnover in brain due to ethanol withdrawal.