垂体腺苷酸环化酶激活肽对实验性冠状动脉粥样硬化家兔心脏胶原网络重塑的作用

目的探讨垂体腺苷酸环化酶激活肽(PACAP)对家兔冠状动脉粥样硬化(AS)进程中心脏胶原网络重塑的作用。方法雄性新西兰家兔60只,随机等分为正常对照组(C组)、AS模型组(A组)和PACAP干预组(P组)。于实验第0、2、4、8、12周末测定血脂含量,并于实验第0、4、8、12周末随机处死每组兔4～6只,定位取带有冠状动脉主干的心脏组织制作石蜡切片,行HE染色和苦味酸-天狼猩红染色,分别在普通光镜和偏光镜下对心肌组织的一般形态和心肌胶原含量及亚型的变化进行定性观察和定量分析。结果①A组和P组血脂水平升高,以A组显著;12周末P组血脂含量显著低于同期A组(P<0.05)。②A组和P组CVF及Ⅰ/Ⅲ型胶原比值均升高,但P组与C组的差别不明显,而A组的差别显著(P<0.05);且P组12周末Ⅰ/Ⅲ型胶原比值明显低于同期A组(P<0.05)。结论PACAP可抑制家兔冠状AS进程中的心脏胶原网络重塑。     

家兔冠状动脉粥样硬化形成过程中心脏的形态重塑

目的研究在体冠状动脉粥样硬化（AS）形成过程中心脏的形态重塑。方法新西兰雄性家兔40只,随机分为正常对照组（C组）及AS模型组（A组）。于实验的第4、8、12周末每组随机处死家兔5～6只,定位取带有冠状动脉主干及分支的心壁全层组织制作石蜡切片,分别行HE、Van Gieson和苦味酸一天狼猩红染色,并在普通和偏振光显微镜下进行定性观察和／或定量分析。结果C组兔心脏标本中未见异常。A组兔位于心外膜的冠状动脉主干及位于心肌间的小分支内,均可见AS斑块;冠状微动脉内虽无明显斑块,但重塑指数增大;心肌细胞最大横径缩小,且心肌间胶原成分增多,尤以Ⅰ型胶原增加明显;至12周末时,上述部分相关指标与同期C组相比具显著性差异（P〈0．05）。结论AS进程中,心组织的形态发生了多方面的重塑性改变,不仅涉及冠状动脉主干及其分支,还包括心肌细胞及间质的改变。     

PACAP保护血管SMC抗LDL损伤的形态学研究

的 :阐明垂体腺苷酸环化酶激活肽 (PACAP)是否对血管平滑肌细胞 (SMC)具有抗损伤保护作用。方法 :以培养的猪肺动脉 SMC为实验对象 ,提取正常人血浆低密度脂蛋白 (L DL )造成细胞的高脂培养环境 ,光镜及电镜下观察 SMC在正常及高脂环境中受 PACAP作用所产生的形态改变。生化方法测定条件培养基中丙二醛 (MDA)的含量。结果 :1L DL 使 SMC的贴壁能力降低 ,细胞外形亦发生极大改变 ;电镜下可见 ,SMC由正常的收缩型变为合成型 ,且细胞膜破坏 ;2 L DL 使 SMC的 MDA产生显著增高 ;3 PACAP可明显减轻 L DL的上述损伤作用。结论 :PACAP可对抗 L DL对 SMC形态和功能的损伤 ,具有 SMC细胞保护作用     

PACAP促PC12细胞突起生长的分子机制

垂体腺苷酸环化酶激活肽 (PACAP)具有广泛的生理功能。近年来的研究发现 ,PACAP具有重要的神经营养作用。 PACAP可通过激活多条细胞内信号转导通路 ,促使 PC12细胞突起生长 ,使其向神经元样细胞分化。本文综述了 PACAP引起 PC12细胞突起生长的信号转导通路 ,有助于深入了解 PACAP神经营养作用的分子机制     

垂体腺苷酸环化酶激活肽对胰腺及其微循环的影响

目的本实验观察外源性垂体腺苷酸环化酶激活肽(PACAP)对正常大鼠胰腺、实验性急性胰腺炎(AP)病程的影响。方法将墨汁灌注的胰腺标本切成20μm厚片 ,二甲苯透明后封片供观察。依照Schmidt-Schnbein的方法 ,以灌流毛细血管长度Lc代表FCD。将OlympusProvisAX70显微镜通过OlympusU -PMTVC与PanasonicBT -H1450Y彩色监视器相连 ,监视器上1cm=12.5μm ;将一打印了12cm×12cm大小、含100个1.2cm×1.2cm方块的网格固定于监视器屏幕。每张切片随机选取5个视野 ,计数毛细血管与网格的交叉点 ,再重复一次 ,然后计算交叉点平均值 ,以此计算灌流毛细血管长度Lc。Lc=π/2Nc/2Pd(Lc单位为cm -1;Nc=交叉点数目 ;P=网格中方块的数目 ;d=网格边缘的长度 )。结果研究发现 ,除蛙皮缩胆囊肽诱发的AP外 ,其余各组机能毛细血管密度 (Functionalcapillarydensity,FCD)均减少。5～30μg/kg的PACAP可促使血清淀粉酶轻微增高、胰腺水肿形成[胰腺干湿比 :实验组(23.88±2.532) %～(25.86±1.974) %与正常组(29.21±5.657) %]、炎性细胞浸润、腺泡细胞空泡化、部分病例可见脂肪坏死和实质坏死灶。15μg/kg和30μg/kgPACAP可加重蛙皮缩胆囊肽诱发的AP,胰腺组织水肿更明显[胰腺干湿比 :实验组(13.45±2.045)%～(17.66±4.652) %与蛙皮缩     

垂体腺苷酸环化酶激活肽对动脉粥样硬化形成过程中脂质过氧化的影响

目的　探讨垂体腺苷酸环化酶激活肽 (PACAP)对家兔实验性动脉粥样硬化 (AS)形成过程中脂质过氧化的影响。方法　 80只雄性新西兰家兔 ,随机分为 3组 :(1)对照组 (C组 ) :喂饲普通颗粒兔饲料 ;(2 )AS模型组 :每只兔每日喂饲含胆固醇 1 5g的颗粒兔饲料 ;(3)PACAP组 (P组 ) :喂饲与AS组同样的饲料 ,另从耳缘静脉注射PACAP。分别于实验的 0、4、8、12周末记录兔体重 ,同时从兔耳中央动脉取空腹血 ,测定丙二醛 (MDA)含量 :并取若干兔的主动脉标本作苏丹Ⅳ染色 ,测量斑块面积。结果　 (1)AS组及P组血清MDA含量均显著高于C组 ;而P组显著低于AS组。 (2 ) 4周末时P组斑块面积显著小于AS组。结论　PACAP具有抗脂质过氧化作用 ,可能与抗AS有关     

冠状动脉硬化斑块与血液动力学及心脏事件关联性分析

目的探讨不同类型冠状动脉斑块与血液动力学及心脏事件之间的关联性。方法回顾临床相关资料,分析冠状动脉螺旋CT成像的软斑块、钙化斑块对血液动力学影响及在诱发心脏事件的差异。结果冠状动脉粥样硬化斑块致血管狭窄程度为20%～40%时,在流经斑块前后速度剖面满足抛物线分布;狭窄程度为50%时,速度剖面紊乱,几乎不呈抛物线分布,分布已不满足层流规律,有回流出现;狭窄程度在50%～75%时,斑块附近管轴上的速度反而比周围的速度小,速度剖面呈中心凹状,在斑块后部呈现明显的回流。软斑块、钙化斑块与心脏事件相关性比较,钙化斑块发生心脏事件93.3%,P〈0.05,具有统计学意义。结论软斑块是可逆转的,对血液动力学无明显影响,但不稳定、易破碎是发生急性冠状动脉综合征关键,是心脏事件发生独立危险因素;钙化斑块是不可逆转的,对血液动力学有明显影响,但斑块稳定、不易破碎是稳定性心绞痛主要诱因,是冠状动脉疾病病程晚期表现。     

垂体腺苷酸环化酶激活肽对胃肠道分泌与运动的影响

垂体腺苷破环化酶激活肽(PACAP)是近年来发现的一种具有多种生物活性的神经肽。它广泛分布于中枢和外周神经系统，以及非神经组织内，它不仅是一种新的下丘脑促垂体激素，而且还是一种新的神经递质和神经调质。此外，它在某些类型细胞的旁分泌和自分泌调节中也发挥作用。本着重介绍PACAP在胃肠道中的分布，对胃肠分泌与运动的影响及与消化系统疾病的关系。     

心脏机械-电反馈对心脏的整合调控作用

心肌的机械活动影响心肌细胞的电活动 ,这一现象被称为心脏机械 电反馈 (MEF)或心脏机电转导。它不但在细胞和器官各个水平上对正常心脏起整合调控作用 ,在病理条件下还与心肌肥厚和某些致死性心律失常的发生有关     

Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes

Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of β-amyloid peptide (Aβ) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Aβ remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Aβ. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Aβ-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.     

Association between pituitary adenylate cyclase-activating polypeptide and thyrotropin-releasing hormone in the rat hypothalamus

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the hypothalamus including the paraventricular nucleus (PVN). In this study the anatomical relationship between PACAP- and thyrotropin-releasing hormone (TRH)-immunoreactive neuronal elements was investigated in the rat hypothalamus. Using a well-characterized mouse monoclonal antibody against PACAP and a rabbit polyclonal antiserum against TRH, we found numerous nerve fibers with PACAP-immunoreactivity (ir) closely apposed to TRH neurons in the PVN suggesting synaptic contacts. Electron microscopy confirmed the presence of synapses between PACAP-ir terminals and TRH-ir perikarya and various dendritic profiles as well as between PACAP-ir terminals and unlabeled perikarya and small- to medium-sized dendrites. Coexistence of the two peptides in perikarya of the PVN was limited to only a few neurons in the periventricular subdivision, but PACAP-ir and TRH-ir extensively coexisted in perikarya of the perifornical cell group, medial preoptic area, lateral hypothalamus and dorsomedial nucleus. The interactions between PACAP-containing neuronal processes and TRH neurons in the PVN raise the possibility that PACAP modulates the secretion of TRH destined for regulation of anterior pituitary TSH. The more general association between PACAP and TRH in other regions of the hypothalamus suggests a further role for PACAP as a cofactor in the function of TRH neurons.     

垂体腺苷酸环化酶激活肽拮抗lactacystin细胞毒性的作用

背景：帕金森病的发病机制未明确,目前尚没有有效的治疗方法能从根本上阻止其病程进展。目的：分析垂体腺苷酸环化酶激活肽对lactacystin诱导的帕金森病多巴胺能PC12细胞凋亡的影响及其分子机制。方法：用神经生长因子将PC12细胞诱导分化成神经元的细胞模型,经不同浓度泛素-蛋白酶体抑制剂lactacystin处理,分别作用不同时间,取细胞存活约为50%的lactacystin作用浓度与时间,建立帕金森病细胞实验模型。实验分组：对照组、lactacystin组、垂体腺苷酸环化酶激活肽1-27干预组(干预1组)、垂体腺苷酸环化酶激活肽1-27和垂体腺苷酸环化酶激活肽6-27共同干预组(干预2组)。观察各组细胞形态变化;MTT法检测细胞活力;免疫印迹(Western blot)法检测内质网应激特异性蛋白caspase-12的表达情况。并观察垂体腺苷酸环化酶激活肽1-26及垂体腺苷酸环化酶激活肽6-27对lactacystin毒性作用的影响。结果与结论：不同浓度及作用时间的lactacystin处理PC12细胞后,细胞活力呈浓度及时间依赖性下降,其中lactacystin 20 μmol/L作用24 h使细胞活力下降约50%。在相同的lactacystin作用条件下(20 μmol/L,24 h),与对照组比较,lactacystin组细胞发生损伤性改变,细胞活力降低,caspase-12活性明显升高(P < 0.01);与lactacystin组比较,干预1组细胞损伤性改变明显好转,细胞活力增强,下调凋亡蛋白caspase-12的表达    (P < 0.01)。干预2组细胞状态则明显不如干预1组,与lactacystin组相差不大。结果提示泛素-蛋白酶体抑制剂lactacystin引起内质网应激导致细胞损伤;垂体腺苷酸环化酶激活肽1-27通过调节上述信号通路发挥保护作用。而作为垂体腺苷酸环化酶激活肽1-27的受体拮抗剂,垂体腺苷酸环化酶激活肽6-27则减弱了垂体腺苷酸环化酶激活肽1-27的这一作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

大鼠三叉神经节垂体腺苷环化酶激活肽免疫反应神经元对松果体的神经支配

目的　证实大鼠松果体的垂体腺苷环化酶激活肽 (PACAP)免疫反应神经纤维来源于三叉神经节神经元。方法　采用颞下窝入路切断大鼠眼 上颌神经 ,存活 3d～ 1周后 ,观察松果体的PACAP免疫反应神经纤维并计数 ,与未经手术的对照组动物比较。结果　在切断了眼 上颌神经的大鼠 ,其松果体的PACAP免疫反应神经纤维明显减少。结论　大鼠三叉神经节是松果体PACAP能神经纤维的主要来源 ,该类神经纤维可能参与调节松果体腺细胞分泌褪黑素     

Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary

In fetal sheep, circulating androgens influence fetal stress responsiveness and the timing of parturition. Nevertheless, little is known about the presence and development of androgen receptors (ARs) in the fetal brain. The present study was undertaken to test the hypothesis that expression of androgen receptor occurs in fetal brain and pituitary, and that the abundance of the AR is ontogenetically regulated. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, and 145-day gestation, and 1 and 7 days postnatal (n=4-5 per group). Using real-time RT-PCR, we measured mRNA expression levels of the receptor in these brain regions and pituitary. In a separate study, we isolated protein from the same brain regions in fetal sheep that were 80 (n=3), 120 (n=4), and 145 (n=4) days. AR mRNA expression in hypothalamus increased in late gestation, starting at 145 days, and increasing progressively after birth. A trend of increasing AR protein in hypothalamus was not significant. AR mRNA expression in pituitary was elevated after 80 days gestation, but with no further increases or decreases in late gestation, while AR protein increased significantly at the end of gestation. In hippocampus and brainstem AR mRNA was constant throughout the latter half of gestation, and AR protein was below the sensitivity of our Western blot assay. We conclude that the fetal brain and pituitary are target sites for circulating androgens or androgen precursors in fetal plasma, and we speculate that the increase in hypothalamic action of androgens immediately prior to birth might be integral to the timing of parturition.     

Light and electron microscopic studies of pituitary adenylate cyclase-activating peptide (PACAP) – immunoreactive neurons in the enteric nervous system of rat small and large intestine

 Pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive (IR) neurons in the myenteric and submucosal plexus of the rat small and large intestine were examined by immunostaining with purified polyclonal antiserum against PACAP (1–15), using both light and electron microscopy. Many PACAP-IR neuronal cell bodies and fibers were found in the myenteric and submucosal plexus. Many of the PACAP-IR fibers originated from the cell bodies of the myenteric and submucosal ganglia. The ganglia were also innervated by PACAP-IR fibers. PACAP-IR fibers penetrated both the circular and longitudinal muscle layers, confirming the previous observations indicating that PACAP neurons act as motor neurons. Ultrastructural study demonstrated that PACAP-IR nerve terminals formed synaptic contacts with PACAP-IR nerve cell bodies or dendritic processes. This observation suggests that PACAP-IR neurons innervate other PACAP-IR neurons, and that PACAP neurons work as interneurons in the enteric nervous system. PACAP-IR nerve cells received not only PACAP-positive nerve terminal input also PACAP-negative nerve terminal input. It also suggests that PACAP neurons are regulated not only by PACAP-IR enteric neurons, but also by neurons originating elsewhere. Our observations support the view that PACAP-IR neurons are involved in the control of gut motility. Accepted: 20 April 1998