P物质刺激脊髓小胶质细胞释放肿瘤坏死因子-α和白细胞介素-1β的作用观察

目的探讨P物质对脊髓小胶质细胞的作用。方法利用原代培养的脊髓小胶质细胞,P物质孵育后采用免疫组织化学方法观察细胞形态学改变,采用酶联免疫吸附试验(ELISA)方法观察细胞释放肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的情况。结果 P物质孵育后,小胶质细胞表现出激活态的形态学改变,400μmol/L和800μmol/L的P物质孵育6 h后,TNF-α和IL-1β释放增多,12 h时达到高峰,之后逐渐下降。结论 P物质作为脊髓水平传递痛信号的重要神经递质,可以刺激活化脊髓小胶质细胞,促进小胶质细胞合成释放TNF-α和IL-1β,并最终促进慢性痛敏的形成。     

咪唑啉类药物对星形胶质细胞白细胞介素-4分泌的作用

目的 观察咪唑啉类药物(咪唑克生,胍丁胺)调节大鼠星形胶质细胞IL-4分泌的影响.方法 10μg·mL-1脂多糖诱导培养后的星形胶质细胞,分为4组:对照组、咪唑克生组、胍丁胺组及地塞米松组.咪唑克生1 mmol·L-1;胍丁胺5 μmol·L-1;地塞米松1 μmol·L-1.于24 h收集上层培养液,用EILSA法测定4组的星形胶质细胞分泌IL-4水平.结果 用咪唑克生、胍丁胺、地塞米松处理后,IL-4分泌均增加.结论 咪唑克生、胍丁胺及地塞米松均促进星形胶质细胞Th2细胞因子分泌,使星形胶质细胞分泌的Th1/Th2细胞因子类型转换,起到免疫调节作用.     

苦参碱对P物质诱导HaCaT细胞表达IFN-γ和IL-10的影响

目的:研究苦参碱对P物质诱导表皮角质形成细胞系HaCaT细胞表达IFN-γ和IL-10的影响。方法:采用ELISA法测定P物质诱导HaCaT细胞分泌IFN-γ和IL-10的时效关系与量效关系。以P物质刺激HaCaT细胞,加入不同剂量的苦参碱共孵育24 h,测定苦参碱对IFN-γ和IL-10表达的影响。结果:以1×10-8mol/L P物质刺激HaCaT细胞24 h,可以显著增加HaCaT细胞IFN-γ和IL-10的分泌量,不同浓度的苦参碱均可以促进HaCaT细胞分泌IFN-γ,其中50μg/mL和100μg/mL的苦参碱均可以显著增加IFN-γ的分泌量;但苦参碱对P物质诱导的IL-10的分泌无显著影响。结论:苦参碱可能通过促进抗炎因子IFN-γ的分泌而发挥抗皮肤变态作用。     

慢性心力衰竭与白细胞介素-17及白细胞介素-10的相关性研究

目的 探讨慢性心力衰竭与白细胞介素(IL)-17、IL-10的相关性.方法 采用酶联免疫吸附试验(ELISA)检测37例慢性心力衰竭患者(慢性心衰组)和34例健康体检者(对照组)血浆IL-17和IL-10水平,并进行相关性分析.结果 慢性心衰组血浆IL-17水平高于对照组[(46.37±10.57) ng/L vs(32.45±4.55)ng/L],IL-10水平低于对照组[(27.49±4.19) ng/L vs(32.71±4.38) ng/L],差异均有统计学意义(t=7.09,5.46,P＜0.01);慢性心力衰竭患者血浆IL-17与IL-10呈负相关(r=-0.63,P＜0.01).结论 慢性心力衰竭的发病可能与体内IL-17、IL-10的水平失衡存在相关.     

白细胞介素5和10在哮喘发病中的作用

气道慢性非特异性炎症是支气管哮喘的重要特征,其病因与发病机制十分复杂,近来Th1/Th2应答失衡在支气管哮喘病理生理过程中的作用越来越受到关注.尤其是细胞因子在哮喘中的作用引起国内外学者的关注,为探讨哮喘的免疫学发病机理,我们在建立大鼠哮喘动物模型的基础上,检测了大鼠血清中白介素5(IL-5)、白介素10(IL-10)的水平[1].     

重组人白细胞介素—10对银屑病患者外周血单个核细胞的作用

免疫学与分子生物学的研究表明,银屑病患者ＣＤ４ Ｔ细胞异常活化,而Ｔｈ２细胞合成与分泌的白细胞介素＿１０（ｉｎｔｅｒｌｅｕｋ＿１０,ＩＬ＿１０）水平降低［１,２］,Ｔｈ１细胞产生的ＩＬ＿２、ＩＦＮ＿γ的ｍＲＮＡ水平明显高于正常人。ＩＬ＿１０是一种具有负向调节免疫功能的细胞因子,可抑制Ｔｈ１细胞增殖与ＩＬ＿２,ＩＦＮ＿γ等细胞因子分泌［３］。本文旨在观察重组人白细胞介素＿１０(ｒｈＩＬ＿１０)体外对银屑病患者外周血中单个核细胞（ＰＢＭＣ）产生有关细胞因子的作用,为临床应用ｒｈＩＬ＿１０治疗银屑病提供依据。…     

小脑星形胶质细胞功能的最新进展

许多研究有助于我们了解小脑星形胶质细胞,特别是伯格曼细胞(BG)。但是,直到最近没人知道它们的功能。在完整小脑内,荧光钙指示器结合星形胶质的标志物SR101多细胞药物填充剂可使星形胶质细胞成像。另外,荧光钙蛋白标记星形胶质细胞的选择靶向作用能够研究它们的功能,不混淆其他神经纤维网的效应与多细胞药物填充和SR101的着色。小脑皮质的2种星形胶质细胞:BG细胞和有缘膜的原浆性星形细胞,在亚细胞水平上钙的浓度到钙的波形,它们显示不同的信号肽指令。许多星形胶质细胞是由嘌呤能物质释放和嘌呤能物质介导所触发的。通过神经元活动和全局血流量的改变证实大量星形胶质细胞的钙浓度是增加。在这篇综述中,概述BG细胞和原浆性胶质细胞的功能。希望一些工具研究它们的钙离子动力学及功能。     

白细胞介素-10的生物学作用及临床应用

白细胞介素 10是一种重要的抑炎性细胞因子 ,对机体的免疫功能和炎症过程具有重要的调节活性。由于国外已经通过Ⅰ期临床进入Ⅱ ,Ⅲ期临床试验 ,本文对国外目前有关其应用研究状况作一综述 ,重点概述了其在消化系统中的应用研究近况 ,并对其生物学作用作一阐述     

白细胞介素-10对大鼠佐剂性关节炎的治疗作用

目的　研究白细胞介素 10 (IL 10 )对大鼠佐剂性关节炎 (AA)的治疗作用及免疫机制。方法　测量非致炎侧足肿胀度、体重、脏器系数 ,采用淋巴细胞增殖法和滑膜成纤维细胞 (SFCs)增殖法测定细胞增殖能力和IL 1产生 ,应用酶联免疫吸附测定法 (ELISA)检测IL 4水平。结果　IL 10(每鼠 2 ,10 μg·d-1× 9d ,ip)能缓解AA病情 ,使足肿胀度降低 ,体重、胸腺和脾脏系数及脾细胞增殖能力得到改善 ,腹腔巨噬细胞 (PMΦ)和滑膜组织细胞 (SMCs)产生IL 1水平下降 ,抑制SFCs和引流淋巴结细胞 (LNCs)过度增殖 ,使LNCs和SMCs产生IL 4水平提高。结论　IL 10能用于大鼠AA的治疗 ,其治疗机制与IL 10、IL 4和某些其它细胞因子介导的免疫调节相关     

纳米氧化钛对大鼠神经胶质细胞的毒性作用

目的研究纳米氧化钛(nano-TiO2)对大鼠神经胶质细胞的毒性作用。方法①体外实验:制备3种粒径10,20和200nm的nano-TiO2颗粒悬液,分别以6.25,12.5,25,50和100mg·L-1对大鼠星形胶质细胞进行72h染毒培养,应用磺基罗丹明B法检测nano-TiO2对星形胶质细胞存活率的影响。②体内实验:Wistar大鼠气管内分别注入上述3种粒径的nano-TiO2悬液,每种粒径设0.1,1.0和10.0mg·kg-13个剂量组,每组3只,72h后分别用电感耦合等离子质谱和放射免疫法检测大鼠脑组织中nano-TiO2的含量和白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和IL-10水平的变化,并通过光学显微镜和透射电镜观察nano-TiO2对大鼠神经胶质细胞形态的影响。结果①体外实验发现,nano-TiO2对大鼠星形胶质细胞存活率的抑制作用具有明显的浓度-效应关系,3种粒径10,20和200nm的nano-TiO2与胶质细胞培养72h,其半数抑制浓度分别为55.9,66.0和3827.0mg·L-1;细胞形态亦发生明显变化,细胞排列稀疏,间隙增大,胞内颗粒物增多,细胞透明度下降。②体内实验发现,粒径10和20nm的nano-TiO20.1mg·kg-1及粒径200nm的nano-TiO20.1,1.0和10.0mg·kg-1组,大鼠脑组织中的nano-TiO2,IL-1β,TNF-α及IL-10浓度与对照组比较无明显变化;粒径10和20nm的nano-TiO21.0及10.0mg·kg-1组大鼠脑组织中nano-TiO2,IL-1β,TNF-α及IL-10浓度随nano-TiO2剂量的增加而增加;病理学观察结果表明,nano-TiO2破坏大鼠血脑屏障,造成脑组织坏死,并进入神经胶质细胞内,引起炎症反应和细胞水肿。结论Nano-TiO2对大鼠神经胶质细胞具有细胞毒性作用,其作用强度与粒径大小有关,其作用机制可能与诱导炎症反应有关。     

Pharmacological regulators of intracellular calcium release channels

Intracellular Ca(2+) release channels, such as inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs), facilitate the release of Ca(2+) from intracellular storage organelles in response to extracellular and intracellular stimuli. Consequently, these large, tetrameric proteins play a central role in Ca(2+) signalling and Ca(2+) homeostasis in virtually all cells. Recent data suggests that intracellular Ca(2+) release channels may also have an important pathophysiological function in certain disease states, including cardiac arrhythmias and heart failure. As a result, there has been much interest in the identification and characterization of novel, selective regulators of these channels. In this article, we review the wide array of pharmacological agents that interact directly with intracellular Ca(2+) release channels and describe the mechanisms underlying their ability to modify channel function.     

NMDA and AMPA receptors mediate intracellular calcium increase in rat cortical astrocytes

INTRODUCTION Almost 50 % of cells in central nervous systemare astrocytes. They play an important role in normalphysiological activity andhave intimate relationship withneurons. There is a close bidirectional communicationexisting between neurons and astrocytes[1]. Glutamate,as the most important excitatory transmitter in centralnervous system, is proved to be a crucial bridge be-tween astrocytes and neurons. Astrocytes respondedto glutamate released from neurons by intracellular C…     

Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes

AIMS: To study the effects of progesterone on contractile activity of smooth muscle strips and on ion currents and intracellular Ca2+ ([Ca2+]i) intensity in single colonic myocytes in guinea pig proximal colons. METHODS: Strips and single cells were dissected from female guinea pig proximal colon. Contraction of strips through an isotonic transducer was assessed and the responsible currents to progesterone were recorded with EPC-9 amplifier in nystatin perforated whole-cell configuration. Detection of [Ca2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. RESULTS: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 microM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (K(Ca)) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% +/- 13% (n = 9, p < 0.01), and to 143% +/- 12% (n = 8, p < 0.01) when perfused with 10 mcM onapristone. Progesterone reduced L-Ca2+ currents to 67% +/- 6% (n = 7, p < 0.01) and had no effect with 5 microM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% +/- 12% (n = 8, p < 0.01). CONCLUSION: Progesterone decreases the contraction of colonic smooth muscles by enhancing K(Ca) currents and reducing Ca2+ influx.     

The effect of lead on calcium release activated calcium influx in primary cultures of human osteoblast-like cells

To further understand the significance of bone as a target tissues of lead toxicity, as well as a reservoir of systemic lead, it is necessary to define the effect of lead on the calcium release activated calcium influx (CRACI) in primary cultures of human osteoblast-like cells (OLC). Pb²⁺ inhibited the immediate CRACI dose-dependent manner. Influx of Pb²⁺ into human OLC was increased dose-dependent manner. The present study demonstrates that the interference of Pb²⁺ with CRACI of human OLC is at least twofold: (1) the initiation of CRACI, i.e., the measurable influx of Ca²⁺ upon Ca²⁺ readdition, is partially inhibited by Pb²⁺ and (2) the influx of Pb²⁺ was enhanced after CRACI had been induced.     

妊高征外周血小板活化和红细胞钙含量的临床分析

目的 探讨不同程度妊高征患者外周血小板活化和红细胞内Ca2+含量(IECa2+)的改变及其临床意义。方法 以三种血小板膜糖蛋白单克隆抗体CD62p、CD61、CD41标记50例正常孕妇和56例妊高征患者外周血小板,并应用Fluo-3/AM导入红细胞,用流式细胞仪检测之水平与Ca2+含量。结果 正常孕妇血小板CD62p、CD61及CD4l的检测值分别为7.16％±3.10％、5.60％±2.78％及8.31％±4.31％;妊高征随程度的加重三种分子呈增高趋势,且重度组检测值显著高于正常组和轻、中度组(P<0.05、P<0.01)。轻度组产前及产时IECa2+与正常妊娠无显著性差异(P>0.05),重度妊高征者增加(P<0.05),IECa2+含量与平均动脉压(MAP)呈正相关,发生胎儿宫内窘迫妊高征患者IECa2+含量较未发生者明显增加(P<0.05)。结论 妊高征外周血小板CD62p、CD61及CD41检测值显著增加,标志着血小板活化程度和凝血能力明显增强,IECa2+增加能够预示胎儿宫内窘迫的发生;采取有效的降压措施可以使IECa2+含量趋于正常水平以减低其危害。     

Extraluminally applied acetylcholine and substance P on the release of EDRF

Acetylcholine, substance P and nitroglycerin applied intra- and extraluminally to the perfused dog femoral artery segment with endothelium caused depressor responses. Endothelium denudation abolished the responses to acetylcholine and substance P. EC50 ratios of extra- versus intraluminal acetylcholine and substance P were 43 and 79, respectively, whereas those of nitroglycerin did not differ. Physostigmine potentiated the response to extraluminal acetylcholine. Acetylcholine seems to be degraded partly by cholinesterase in the arterial wall. Acetylcholine and substance P applied extraluminally are expected to reach the endothelium and release endothelium-derived relaxing factor.     

Stress-induced release of substance P in the locus coeruleus modulates cortical noradrenaline release

Several lines of evidence implicate the neuropeptide substance P (SP) in the modulation of emotional behavior. Interaction between SP and noradrenergic systems has been proposed to be important in the regulation of stress, depression, and anxiety mechanisms; however, most evidence so far is based on studies in unchallenged and/or anesthetized animals. Thus, by using a dual-probe microdialysis approach in freely moving animals, the aim of the present study was to investigate whether a relevant stressor can trigger the release of SP in the locus coeruleus (LC) and whether and how this response modulates noradrenaline (NA) transmission both in the LC and in the medial prefrontal cortex (mPFC), an important LC terminal region involved in emotional processing. While confirming previous reports that neurokinin 1 receptor (NK1R) antagonists activate cortical noradrenergic transmission under resting conditions, we present evidence that this interaction is opposite during stress challenge. Our results show that exposure to forced swimming considerably enhanced the release of SP and NA in the LC. Administration of a selective NK1R antagonist into the LC potentiated this NA response within the LC but abolished the stress-induced increase in NA release within the mPFC. These findings demonstrate stress-induced increase in endogenous extracellular SP levels within the LC exerting a facilitatory effect on the noradrenergic pathway to the mPFC. The attenuation of stress-induced hyperactivation of this pathway by NK1R antagonists, presumably via enhancing NA and autoinhibition in the LC, may contribute to the therapeutic efficacy of these drugs known to ameliorate symptoms of stress-related disorders.     

The effects of HGCl2 and mersalyl on mechanisms regulating intracellular calcium and transmitter release.

HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lower concentrations of HgCl2 showed a stimulatory effect on mitochondrial calcium uptake. It is suggested that the effect of mercurials on transmitter release is mediated via changes of the intracellular calcium ion concentration.     

Role of intracellular calcium in histamine release from rat mast cells

An aqueous extract of Panax Ginseng C.A. Meyer (G.S.) was prepared by boiling crushed G.S. roots in water. The extract obtained was adjusted to 125 mg G.S. per ml and was administered orally to mice for 5 to 6 days at the daily dose of 10, 50 and 250 mg G.S. per kg or was added to cultures of mouse spleen cells at concentrations varying between 0.25 and 8 mg G.S. per ml. The average total ginsenoside content of the G.S. roots used was determined by HPLC analysis and found to be 0.58% (w/w). Treated mice responded with enhanced antibody formation to either a primary or a secondary challenge with sheep red cells. The effects were dose-dependent. At the highest dose regimen, the primary IgM response was increased by 50% and the secondary IgG and IgM responses were increased by 50 and 100%, respectively. An even more pronounced effect was obtained with natural killer cell activity which was enhanced between 44 and 150% depending on the effector-to-target cell ratios used in the assay. In vitro, G.S. showed two main effects, an inhibition of stimulated and spontaneous lymphocyte proliferation at high, but not cytotoxic concentrations and an enhancement of interferon production particularly in non-stimulated spleen cells. The immunostimulating effects obtained in vivo are in agreement with the stimulation of interferon production observed in vitro. The inhibition of lymphocyte proliferation, however, cannot be reconciled with the immunostimulatory action of G.S. observed in vivo.     

Postglomerular vasoconstriction to angiotensin II and norepinephrine depends on intracellular calcium release

The current study was performed to determine the effect of calcium store depletion with cyclopiazonic acid (CPA) on the pre- and postglomerular vasoconstrictor responses to angiotensin II (ANG II) and norepinephrine (NE). CPA treatment significantly attenuated the afferent arteriolar response to 10 nM ANG II by 51% and to 1000 nM NE by 19%. Efferent arteriolar responses to ANG II and NE were also greatly attenuated in the presence of CPA. These data demonstrate that afferent and efferent arteriolar responses to ANG II and NE depend on release of calcium from CPA-sensitive intracellular stores. Furthermore, the postglomerular response to these agents exhibits a greater dependency on calcium release from intracellular stores.