纳络酮对缺氧缺血性脑病新生儿NPY、β-EP、NSE和炎症因子表达的影响

目的探讨纳络酮对缺氧缺血性脑病新生儿NPY、β-EP、NSE和炎症因子表达的影响。方法将54例缺氧缺血性脑病新生儿随机分为对照组27例和观察组27例。对照组进行常规缺氧缺血性脑病治疗,观察组在常规治疗基础上加用纳洛酮进行治疗。比较2组患儿治疗前和治疗后1、2、3 d的血清NPY、β-EP、NSE和促炎介质、抑炎介质水平。结果治疗后1、2、3 d,观察组的血清NPY、β-EP、NSE和促炎介质、抑炎介质水平均显著低于对照组(P0.05)。结论纳络酮能积极改善缺氧缺血性脑病新生儿NPY、β-EP、NSE和炎症因子的表达。     

肥胖代谢调控因子——人神经肽Y及受体生物学特性的分子水平研究

肥胖代谢调控因子人神经肽Y及其生物衍作为神经递质及生物效应分子可通过不同亲和力及特异性作用于相应靶细胞膜上至少4种人神经肽Y受体Y1R、Y2R、Y4R、Y5R,并通过人神经肽Y配体和受体的特异性结合,激活相关细胞信号传导通路,参与或刺激相关细胞的增殖和分化及内分泌激素的合成与分泌,进而调控整个机体或局部组织各种生理功能,直接或间接影响包括老年机体在内的多种代谢变化及某些老年病的发生、发展、变化及转归,因此成为老年生物学和老年医学研究的热点。本文从人神经肽Y及其受体的生物学特性和分子水平出发,对NPY配体及其受体的分子结构、生物学特性及相互作用机制进行综述,为今后系统阐述该配体和受体在老年病中的代谢特点和作用规律奠定理论基础。     

The different time courses of reading different levels of Chinese characters: an ERP study

AMP-activated protein kinase (AMPK) is an energy sensor that is activated by the increase of intracellular AMP:ATP ratio. AMPK in the hypothalamic arcuate nucleus (ARC) is activated during fasting and the activation of AMPK stimulates food intake. To clarify the pathway underlying AMPK-induced feeding, we monitored the activity of single ARC neurons by measuring cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2 fluorescence imaging. An AMPK activator, AICA-riboside (AICAR), at 200 μM increased [Ca(2+)](i) in 24% of ARC neurons. AMPK and acetyl CoA carboxylase were phosphorylated in the neurons with [Ca(2+)](i) responses to AICAR. AICAR-induced [Ca(2+)](i) increases were inhibited by Ca(2+)-free condition but not by thapsigargin, suggesting that AICAR increases [Ca(2+)](i) through Ca(2+) influx from extracellular space. Among AICAR-responding ARC neurons, 38% were neuropeptide Y (NPY)-immunoreactive neurons while no proopiomelanocortin (POMC)-immunoreactive neuron was observed. Intracerebroventricular administration of AICAR increased food intake, and the AICAR-induced food intake was abolished by the co-administration of NPY Y1 receptor antagonist, 1229U91. These results indicate that the activation of AMPK leads to the activation of ARC NPY neurons through Ca(2+) influx, thereby causing NPY-dependent food intake. These mechanisms could be implicated in the stimulation of food intake by physiological orexigenic substances.     

丹参注射液联合小剂量多巴胺对老年脑外伤大鼠肾功能的影响

目的：研究丹参注射液联合小剂量多巴胺对老年脑外伤大鼠肾功能的影响。方法：将50只24月龄Wistar大鼠随机分为对照组和创伤组,其中创伤组又分为多巴胺治疗组、丹参治疗组、多巴胺联合丹参治疗组和创伤未治疗组。创伤组大鼠采用重度自由落体建立脑创伤模型,分别给予相应治疗,24h后检测各组血清尿素氮（BUN）、肌酐（Scr）值和神经肽Y（neuropeptide Y,NPY）含量,计算内生肌酐清除率（Ccr）,并观察肾组织苏木素-伊红（HE）染色的病理形态学变化。结果：各创伤治疗组血清BUN、Scr、Ccr值和NPY含量均高于对照组（P〈0.05）,HE染色观察显示脑外伤后肾组织发生病理损伤改变;联合治疗组BUN、Scr、Ccr值和血清NPY含量低于创伤未治疗组（P〈0.05）;丹参治疗组和多巴胺治疗组血清BUN、Scr、Ccr值低于创伤未治疗组（P〈0.05）,而血清NPY含量与创伤未治疗组比较差异无统计学意义（P〉0.05）;丹参治疗组和多巴胺治疗组血清BUN、Scr、Ccr值和NPY含量之间差异无统计学意义（P〉0.05）。经直线相关分析显示,血清NPY含量与血清BUN和Scr变化呈正相关（r分别为0.818和0.735,P〈0.05）,与Ccr变化呈负相关（r=-0.861,P〈0.05）。结论：老年脑外伤后血清NPY含量升高可能参与了继发肾功能损害的过程,丹参注射液联合小剂量多巴胺可通过降低老年脑外伤后血清NPY的含量而具有对肾功能的保护作用,较单独使用丹参或多巴胺治疗效果为佳。     

Gut hormones and appetite control

Many peptides are synthesized and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Our understanding of how neurohormonal gut-brain signaling regulates energy homeostasis has advanced significantly in recent years. Ghrelin is an orexigenic peptide produced by the stomach, which appears to act as a meal initiator. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Recent research suggests that gut hormones can be manipulated to regulate energy balance in humans, and that obese subjects retain sensitivity to the actions of gut hormones. Gut hormone-based therapies may thus provide an effective and well-tolerated treatment for obesity.     

The role of CNS fuel sensing in energy and glucose regulation

Individual cells must carefully regulate their energy flux to ensure nutrient levels are adequate to maintain normal cellular activity. The same principle holds in multicellular organisms. Thus, for mammals to perform necessary physiological functions, sufficient nutrients need to be available. It is more complex, however, to understand how the energy status of different cells impacts on the overall energy balance of the entire organism. We propose that the central nervous system is the critical organ for the coordination of intracellular metabolic processes that are essential to guarantee energy homeostasis at the organismal level. In particular, we suggest that in specific hypothalamic neurons, evolutionarily conserved fuel sensors, such as adenosine monophosphate-activated protein kinase and mammalian target of rapamycin (mTOR), integrate sensory input from nutrients, including those derived from recently ingested food or those that are stored in adipose tissue, to regulate effector pathways responsible for fuel intake and utilization. The corollary to this hypothesis is that dysregulation of these fuel-sensing mechanisms in the brain may contribute to metabolic dysregulation underlying diseases, such as obesity and type 2 diabetes.     

Infusion of neuropeptide Y into CA3 region of hippocampus produces antidepressant-like effect via Y1 receptor

A couple of papers indicate that patients with depression show a decrease in serum neuropeptide Y (NPY). To study the role of NPY in depression, we examined the effects of infusion of NPY into the hippocampus of learned helplessness (LH) rats (an animal model of depression). Infusion of NPY into the cerebral ventricle of LH rats showed antidepressant-like effects. Infusion of NPY into the CA3 region, but not the dentate gyrus (DG), produced antidepressant-like effects in the LH paradigm. Infusion of NPY did not affect locomotor activity or aversive learning ability. Coadministration of BIBO3304 (a Y1 receptor antagonist) with NPY to the CA3 region blocked the antidepressant-like effects of NPY, whereas coadministration of NPY with BIIE0246 (a Y2 receptor antagonist) to the CA3 region failed to block antidepressant-like effects. Furthermore, infusions of [Leu(31) Pro(34)]PYY (a Y1 and Y5 receptor agonist) alone and BIIE0246 alone into the CA3 region produced the antidepressant-like effects in LH rats. These results suggest that infusion of NPY into the CA3 region of hippocampus of LH rats produces antidepressant-like activity through Y1 receptors and attenuating effects through Y2 receptors.     

Neuropeptide Y stimulates proliferation, migration and differentiation of neural precursors from the subventricular zone in adult mice

The neuropeptide Y (NPY) is widely expressed in the central nervous system and has been shown to stimulate neurogenesis in the hippocampus and the olfactory epithelium. Here, we demonstrate that intracerebroventricular injection of NPY stimulates proliferation of neural precursors in the mice subventricular zone (SVZ), one the most neurogenic areas of the brain. Newly generated neuroblasts migrate through the rostral migratory stream to the olfactory bulb and also directly to the striatum, as evidenced by BrdU labelling and cell phenotyping. Using knock-out mice, specific NPY receptor agonists and antagonists, we report that this neuroproliferative effect is mediated by the Y1 receptor subtype that we found to be highly expressed in the SVZ both at the mRNA and protein levels. Our data suggest that stimulating endogenous SVZ neural stem cells by NPY may be of a potential interest in cell replacement based therapies of neurodegenerative diseases affecting the striatum such as Huntington's disease.