全身炎症反应中脂蛋白与细胞因子关系及其对预后影响

目的 研究全身炎症反应综合征(SIRS)患者血清脂蛋白水平与细胞因子水平的相关性及在预后中的预测价值。方法 检测SIRS患者血清脂蛋白与细胞因子TNFα、IL-6水平进行相关性分析，并分析脂蛋白水平与预后的相关性。结果 SIRS患者血清HDL、LDL与TNFα水平均呈显著性负相关，而CH和TG与TNFα的相关性无显著意义；血清HDL、LDL、CH和TG与IL-6水平均呈一定程度的负相关，但无显著意义；血清HDL、LDL与SIRS的预后有显著相关。结论 SIRS患者血清脂蛋白与细胞因子水平呈一定程度负相关，血清脂蛋白水平可能对SIRS的预后有一定的预测作用。     

银杏达莫对冠心病患者血清炎症细胞因子的影响

研究表明,冠心病(CHD)与炎症反应有关.细胞间黏附因子1(ICAM-1)和TNF-α是两种关键的炎症细胞因子,在CHD发病中起重要作用.银杏达莫具有抗凝、扩张冠脉血管及脑血管、改善脑缺血症状和记忆功能的作用.为探讨银杏达莫对CHD患者血清炎症细胞因子的影响,我们进行了相关研究.现报告如下.     

胸腺肽对慢性乙肝患者血清细胞因子含量的影响

目的 观察大剂量国产胸腺肽对慢性活动性乙肝患者血清细胞因子的影响,探讨胸腺肽治疗慢性乙肝的机制。方法 选择慢性活动性乙肝患者３４例,分成两组：胸腺肽组１９例,一般护肝组１５例。比较观察治疗前后患者血清ＩＦＮ－α、ｓＩＬ－２ｒ、ＴＮＦ和β２－ＭＧ为指标的变化。结果 胸腺肽治疗后,患者ＰＢＭＣ ＩＦＮ－α诱生能力较治疗前上升１１９．９９％,血清ｓＩＬ－２ｒ和ＴＮＦ含量分别下降了３５．５６％和４１．８０     

男性糖尿病患者血清睾酮、细胞因子水平改变对骨密度的影响

2002年1月至2003年1月，我们应用双能X线骨密度仪测定45例男性2型糖尿病(T2DM)患者桡骨远端骨密度(BMD)，并检测其细胞因子白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-a(TNF-a)、胰岛素样生长因子-1(IGF-1)及血清睾酮(T)水平，旨在探讨T2DM患者骨改变及其发病机制，为临床防治提供参考。     

艾地苯醌对缺血性脑卒中后抑郁患者血清神经细胞因子、单胺类递质代谢及炎症反应的影响

目的探讨艾地苯醌对缺血性脑卒中后抑郁患者血清神经细胞因子、单胺类递质代谢及炎症反应的影响。方法收集该院2013年6月至2015年6月收治的缺血性脑卒中后抑郁患者72例,随机分为研究组(36例,艾地苯醌治疗)和对照组(36例,安慰剂治疗)。检测两组患者术前、术后8 w脑源性神经营养因子(BDNF)、神经生长因子(NGF)、5-羟色胺(HT)、5-羟吲哚乙酸(HIAA)、去甲肾上腺素(NE)、白细胞介素(IL)-6、IL-23、肿瘤坏死因子(TNF)-α水平。结果治疗前,两组各检测指标均无统计学差异(P0.05);治疗后,研究组BDNF、NGF水平均高于对照组(P0.05);5-HT、NE水平高于对照组,5-HIAA水平低于对照组(P0.05);IL-6、IL-23及TNF-α水平均低于对照组(P0.05)。结论艾地苯醌治疗可以增加缺血性脑卒中后抑郁患者神经细胞因子含量,改善单胺类递质代谢,缓解炎症反应,值得临床推广。     

鼠白细胞介素12质粒对小鼠支气管哮喘模型气道炎症及细胞因子的影响

目的　研究鼠白细胞介素 12 (IL 12 )基因表达 (mIL 12 )质粒对小鼠支气管哮喘 (简称哮喘 )模型气道炎症及细胞因子的影响 ,并分析其作用机制。方法　卵白蛋白 (OVA)致敏建立小鼠哮喘模型。BALB/c小鼠 4 1只 ,分为 6组。即哮喘模型组 (A组 ) 8只 :OVA致敏 +OVA气雾攻击 ;模型对照组 (B组 ) 6只 :用生理盐水代替 1%OVA溶液雾化 ,余处理同A组 ;mIL 12质粒预防组 (C组 ) 8只 :实验第 1、3、5天各肌肉注射mIL 12质粒 10 0 μg ;mIL 12质粒治疗组 (D组 ) 8只 :实验第 14、16、18天各肌肉注射mIL 12质粒 10 0 μg ;空质粒预防组 (E组 ) 5只 :实验第 1、3、5天各肌肉注射空质粒 10 0 μg ;空质粒治疗组 (F组 ) 6只 :实验第 14、16、18天各肌肉注射空质粒 10 0 μg。测定所有小鼠支气管 肺泡灌洗液 (BALF)中的嗜酸粒细胞 (EOS)个数和IL 4、IL 5、γ干扰素 (IFN γ)水平。结果B组小鼠EOS个数和IL 4、IL 5、IFN γ浓度分别为 (0 0 1± 0 0 3)× 10 8/L、(2 4± 4 ) pg/ml、(33± 6 ) pg/ml、(72 5± 5 9) pg/ml,C组为 (0 0 6± 0 0 4 )× 10 8/L、(43± 13) pg/ml、(6 3± 10 )pg/ml、(6 2 6± 6 0 ) pg/ml,D组为 (0 11± 0 12 )× 10 8/L、(38± 14 )pg/ml、(6 6± 14 ) pg/ml、(6 6 1± 4 0 ) pg/ml,与A     

连续性血液净化对全身炎症反应综合征患者血浆细胞因子水平的影响

连续性血液净化 (CBP)治疗各种危重症疾病疗效显著 ,但有关CBP对各种致病因子的清除以及对血中这些因子浓度的影响 ,文献报道结果不一。我们对 13例严重全身炎症反应综合征 (SIRS)患者连续性替代肾脏治疗 (CRRT)治疗前后的 5种细胞因子浓度进行检测 ,并探讨其变化的临床意义。对象与方法1.对象 :13例SIRS患者 ,男性 7例 ,女性 6例 ,年龄 2 5～ 75岁 ,平均年龄 5 2岁。其中感染性休克 5例 ,急性呼吸窘迫综合征 3例 ,急性胰腺炎 3例 ,多发伤 2例。所有患者均符合SIRS诊断标准[1] 。2 .方法 :( 1)CBP检测全部病例均使用B .BRAUNDi…     

银杏叶提取物对慢性乙型肝炎患者血清纤维化指标及细胞因子的影响

目的观察银杏叶提取物(Ginkgo Biloba extract,EGb)对慢性乙型肝炎患者肝纤维化指标及细胞因子的影响。方法60例慢性乙型肝炎患者随机分为治疗组(一般保肝治疗 EGb组)和对照组(一般保肝治疗组),治疗前后检测肝功能,用放射免疫法检测血清肝纤维化指标,Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CIV)、透明质酸(HA)、层黏蛋白(LN),应用ELISA法检测血清PAF、S-ICAM、TGF-β1。结果治疗组治疗后血清PCⅢ、CIV、HA、LN、TGF-β1及PAF水平较治疗前及对照组治疗后均显著降低(P<0.05或P<0.01)。结论银杏叶提取物通过影响慢性乙型肝炎患者血清细胞因子、PAF、TGF-β1发挥抗肝纤维化作用。     

左归丸对老年性痴呆模型鼠脑神经元HSP70及超微结构的影响

目的 探讨左归丸对老年性痴呆(Alzheimer病,AD)动物模型HSPT0及超微结构的影响.方法 模型组以D-半乳糖腹腔注射合并A13注射海马制备AD动物模型,各治疗组分别在造模的同时灌胃左归丸和抗脑衰胶囊、哈伯因.采用生化法检测各组大鼠脑匀浆AchE,运用RT-PCR测定各组海马HSP70的表达并用透射电镜观察各组海马神经元超微结构的变化.结果 左归丸能明显抑制模型鼠脑组织中AchE活性,上调HSP70的表达,抑制细胞凋亡.超微结构观察发现模型组海马神经元显现凋亡早期的形态特点,各治疗组和对照组对凋亡皆有抑制作用.结论 左归丸对痴呆鼠海马神经元细胞凋亡有抑制作用,其机制可能与其抑制模型鼠脑组织中AchE活性、上调HSP70的表达和改善神经元细胞损害有关.     

Hepatic stellate cells express Ca2+ pump-ATPase and Ca2+-Mg2+-ATPase in plasma membrane of caveolae

Intracytoplasmic free calcium ions (Ca²⁺) are maintained at a very low concentration in mammalian tissue by the extrusion of Ca²⁺ across a steep extracellular Ca²⁺ gradient, mainly through the activity of plasma membrane Ca²⁺ pump-ATPase. The present study aimed to identify, by electron cytochemical and electron immunogold methods, the ultrastructural localizations of two types of plasma membrane Ca²⁺-ATPase; Ca²⁺-Mg²⁺-ATPase and Ca²⁺ pump-ATPase, in hepatic stellate cells. Liver tissues and isolated hepatic stellate cells (HSCs) were studied. The ultrastructural localization of Ca²⁺-Mg²⁺-ATPase activity was examined by the electron cytochemical method of Ando. The localization of Ca²⁺ pump-ATPase was identified by immunofluorescence. The ultrastructural localization of Ca²⁺ pump-ATPase was identified by the electron immunogold method. The cytochemical reaction products of Ca²⁺-Mg²⁺-ATPase activity were localized on the outer (cavity) side of the plasma membrane of caveolae. Immunofluorescence of Ca²⁺ pump-ATPase was seen as small dots along the cell edge in HSCs. Immunogold particles indicating the presence of Ca²⁺ pump-ATPase were identified on the inner (cytoplasmic) side of the plasma membrane of caveolae. We localized Ca²⁺ pump-ATPase on the inner side of the plasma membrane caveolae and Ca²⁺-Mg²⁺-ATPase on the outer leaflet of the caveolar plasma membrane in stellate cells, suggesting that Ca²⁺ pump-ATPase may play a key role in the Ca²⁺ reflux. Received: March 7, 2000 / Accepted: July 7, 2000     

Sickle red cell calcium metabolism: studies on Ca2+-Mg2+ATPase and Ca-binding properties of sickle red cell membranes

Sickle (Hb SS) red cells, preloaded with 45Ca by reversal of hemolysis, exhibit an incomplete 45Ca extrusion, retaining approximately four times more 45Ca than normal cells. Studies indicated that neither the reduction in Hb SS cell Ca2+-Mg2+ ATPase activity (84% of normal) nor the activation of Ca2+-Mg2+ ATPase by calmodulin was sufficiently different from normal cells to attribute a major role to the calcium pump in 45Ca retention. These results suggested that 45Ca retention may reflect an alteration in the calcium-binding properties of Hb SS cell membranes. Low-affinity calcium-binding (freely dissociable) was similar in normal and Hb SS cell membranes. However, the total calcium bound with high-affinity (tightly bound) was four-to-five times greater in Hb SS cell membranes than in normal membranes. These results are compatible with the hypothesis that Hb SS cell 45Ca retention reflects an exchange of a fraction of the total 45Ca with a tightly bound calcium pool, larger in Hb SS cell membranes than in normal membranes. A comparable degree of red cell 45Ca retention, which did not correlate with the reticulocyte population, was observed in other chronic anemic states. These findings suggest that the increased high-affinity calcium binding by the membrane may be a consequence of cellular changes induced by the anemic condition.     

Age-related alterations in Ca2+ signals and mitochondrial membrane potential in exocrine cells are prevented by melatonin

Abstract:  Information regarding age-induced Ca²⁺ signal alterations in nonexcitable cells is limited. In addition, little evidence exists on the ability of melatonin to palliate the effects of aging on Ca²⁺ signals and mitochondrial potential, a parameter involved in both Ca²⁺ signaling and aging. We studied the ability of melatonin to prevent the effects of aging on intracellular Ca²⁺ homeostasis and mitochondrial potential in exocrine cells. Pancreatic acinar cells were obtained from adult (3 months old) and aged (22–24 months old) mice by collagenase dispersion. Ca²⁺ signals, in situ mitochondrial potential and in vitro amylase secretion were determined. Secretion in response to increasing levels of the secretagogues, acetylcholine and cholecystokinin (CCK), were impaired in aged pancreatic acini. This decrease was accompanied by an inhibition in the amplitude of the peak response to maximal concentrations of the agonists, and by a decrease in the pattern of Ca²⁺ oscillations induced by postprandial levels of CCK. Both the size of the calcium pools, assessed by low levels of ionomycin, and capacitative calcium entry, induced by depletion of the stores with thapsigargin, were diminished in aged cells. These changes in Ca²⁺ homeostasis were associated with depolarization of intracellular mitochondria. Oral administration of melatonin for 3 months to aged mice restored the secretory response, the amplitude and frequency of Ca²⁺ responses, the size of intracellular calcium pools, the capacitative calcium entry, and the mitochondrial potential. In conclusion, melatonin restores secretory function, Ca²⁺ signals and mitochondrial potential of aged exocrine cells.     

The H2O2-Generating Enzyme,Xanthine Oxidase,Decreases Luminal Ca2+ Content of the IP3-Sensitive Ca2+ Store in Vascular Endothelial Cells

Objective: Xanthine oxidase inhibits agonist-stimulated Ca²⁺ signaling in calf pulmonary artery endothelial cells by an H₂O₂-dependent mechanism. We investigated the effect of xanthine oxidase on luminal Ca²⁺ content of the inositol-1,4,5-trisphosphate (IP₃)-sensitive Ca²⁺ store. Methods: Luminal Ca²⁺ content was estimated from the net release of Ca²⁺ activated by 2,5-di-t-butylhydroquinone (BHQ), an inhibitor of microsomal Ca²⁺ pumps. Results: Initially, xanthine oxidase depleted the IP₃-sensitive Ca²⁺ store of releasable Ca²⁺, but with more prolonged incubation, the enzyme also depleted non-IP₃-sensitive stores. In addition, xanthine oxidase inhibited capacitative Ca²⁺ influx. Similar results were observed when thapsigargin was substituted for BHQ. Conclusions: Depletion of luminal Ca²⁺ content within the IP₃-sensitive Ca²⁺ store contributes to xanthine oxidase inhibition of Ca²⁺ signaling in vascular endothelial cells.     

耶尔森氏菌属45Mdal质粒与Ca^2＋依赖性

本文检查了鼠疫菌，假结核菌和小肠结肠炎菌的质粒ＤＮＡ，并观察了它们的Ｃａ＾２＋依赖性。结果表明Ｌｃｒ与它们共有的４５Ｍｄａｌ质粒相关，但也存在有４５Ｍｄａｌ质粒而菌株为Ｌｃｒ＾－，或查不到４５Ｍｄａｌ质粒而菌株表现Ｌｃｒ＾＋。初步分析认为，前者可能是介导式操纵钙依赖性的基因失活，而后者可能是４５Ｍｄａｌ质粒整合在染色体上。     

High glucose level inhibits capacitative Ca2 + influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism

Summary In cultured mesangial cells (MC), capacitative Ca^{2 +} influx via store-operated channels (SOC) is potentiated by agents that release Ca^{2 +} from intracellular stores, and inhibited by protein kinase C (PKC). Cells grown under high glucose conditions, as a model of the diabetic microenvironment, display reduced Ca^{2 +} signalling in response to vasoconstrictors, probably due to downregulation by elevated PKC activity. Since SOC might be relevant to this phenomenon, we assessed Ca^{2 +} influx by microfluorometry of fura-2-loaded rat MC cultured for 5 days in normal (5.5 mmol/l, NG) or high glucose (30 mmol/l, HG). The addition of 1–10 mmol/l Ca^{2 +} to NG cells equilibrated in Ca^{2 +} -free media induced an immediate Ca^{2 +} influx with a free cytosolic Ca^{2 +} ([Ca^{2 +} ]_i) plateau of 155 ± 50 and 318 ± 114 nmol/l, respectively. Basal influx was reduced to 88 ± 8 and 145 ± 17 nmol/l [Ca^{2 +} ]i (1–10 mmol/l Ca^{2 +} , p < 0.01) by 30 mmol/l d-glucose. This effect of HG was confirmed by Mn^{2 +} quenching of fura-2, indicating reduced entry of divalent cations via the capacitative pathway. Equimolar l-glucose had no effect on Ca^{2 +} influx, consistent with a non-osmotic mechanism. Arginine vasopressin (10 μmol/l) elicited weaker release of stored Ca^{2 +} and subsequent influx in HG cells (191 ± 33 vs 153 ± 24 nmol/l, 400 ± 76 vs 260 ± 33 nmol/l, 1–10 mmol/l Ca^{2 +} , NG/HG, p < 0.05). To examine the involvement of PKC in the effect of HG on capacitative Ca^{2 +} influx, the enzyme was activated or downregulated by treatment with 0.1 μmol/l phorbol myristate acetate (PMA) for 3 min or 24 h, respectively. PMA acutely inhibited Ca^{2 +} influx in NG cells, while PKC downregulation restored it in HG cells. Similarly, the PKC inhibitors staurosporin or H-7 normalized SOC activity in HG cells. In summary, impairment of Ca^{2 +} influx via SOC by HG is one mechanism of the reduced MC [Ca^{2 +} ]_i responsiveness to vasoconstrictors. This event is mediated by PKC and may contribute to the glomerular haemodynamic changes in the initial stages of diabetes mellitus. [Diabetologia (1997) 40: 521–527] Received: 25 November 1996 and in revised form: 30 January 1997     

蛋白激酶C和Ca2+在心肌细胞预处理中的作用

目的：探讨心肌细胞缺氧预处理、蛋白激酶C（PKC）和细胞内钙离子在心肌细胞预处理中的作用。方法：在培养乳鼠心肌细胞缺氧预处理的模型上，观察缺氧预处理以及PKC抑制剂Chelerythrine和钙离子螯合剂BAPTA／AM对缺氧预处理的影响。结果：缺氧预处理可以减少缺氧／复氧对心肌细胞的损伤。PKC抑制剂Chelerythrine和钙离子螯合剂BAPTA／AM可以抑制缺氧预处理的心肌保护作用。结论：PKC和钙离子介导心肌细胞的缺氧预处理。     

异丙肾上腺素对心肌细胞内钙释放和肌浆网内钙容量的影响

目的 :心肌细胞膜上的 β-肾上腺素受体的激活对兴奋 -收缩耦联 （ECC）过程有重要的调节作用。本课题利用异丙肾上腺素 （ISO,1μmol/ L）激活 β-肾上腺素受体从而研究其对源自心肌细胞肌浆网的胞内钙释放 （ECC的重要环节 ）和肌浆网内钙容量的影响 ,进而分析钙释放与钙容量之间的关系。方法 :局部场刺激作用于成年大鼠心肌细胞 ,促使后者产生动作电位 ,进而诱发胞内钙瞬变 （ACT） ,由 ACT可估测胞内钙释放。肌浆网内钙容量则由咖啡因 （2 0 m mol/ L）诱发的钙瞬变 （CCT）估测。实验结果均由 Zeiss L SM- 5 10激光共聚焦显微镜系统记录。结果 :ISO作用下的 ACT峰值为 10 .2 9± 0 .35 （n=13）比正常情况下的 5 .74± 0 .2 7（n=18）高 （P<0 .0 1）。 ISO作用下的CCT峰值为 11.2 3± 0 .2 9（n=13）比正常情况下的 7.6 2± 0 .2 4 （n=18）高 （P<0 .0 1）。结论 :ISO可明显地提高心肌细胞内钙释放量和肌浆网内的钙容量。不管有无 ISO存在 ,胞内钙释放量总是只占肌浆网内钙容量的一部分。在正常情况下 ,心肌的钙释放量有较大的储备能力 ,且此储备可因β-肾上腺素受体的激活而动员。     

冠状动脉平滑肌细胞大电导钙离子激活钾通道电流的特点

Objective To investigate characteristics of large conductance Ca2+ -activated K+ currents ( BK currents) in normal rat coronary smooth muscle cells. Methods Coronary smooth muscle cells were isolated by enzyme digestion. Potassium channels in coronary smooth muscle cells were identified by applications of different potassium blockers. BK currents were recorded by patch clamp in whole ce11 and single channel configuration,respectively. BK currents amplitude and conductance were calculated. Voltage-sensitive and calciumsensitive characteristics of BK currents and changes with IBTX,a specific blocker,were observed. Results BK currents in normal smooth muscle cells accounted for 65% ± 4% of total potassium currents( n = 12), BK current conductance was (258 ± 42) pS ( n = 6), and current densities were ( 275 ± 40 ) pA/pF at voltage 150 mV ( n = 8). Open probabilities ( NP0 ) of BK channels at calcium 1 μmol/L in external solution and test potentials at 0,20,40,60,80,100,120,140 and 160 mV were 0,0. 0002,0. 0016 ± 0. 0005,0. 0283 ± 0. 0081,0. 05694 ±0. 0102,0. 3533 ± 0. 0514,1. 4922 ± 0. 1578,2. 5975 ± 0. 3632, and 4. 6041 ± 0. 7834, respectively (P＜0.05,n =5). NP0 of BK channels at test potential 60 mV,and calcium in external solution at 0,0. 001,0. 01,0. 1,1,10,50 and 100 μmol/L were 0,0.0001,0.0031 ± 0.0008,0.0042 ± 0.0090,0.0808 ± 0.0105,0.7591 ±0. 1274,2.7242 ±0.4612,and 3.2366 ±0.5728,respectively(P ＜0.05,n =6). Conclusion BK channels are widely distributed in normal coronary smooth muscle cells, have voltage-sensitive and calcium-sensitive characteristics, and play an important role in regulation of coronary vascular tension.     

Acute and chronic effect of alcohol on Ca2+ channels in hepatic stellate cells

BACKGROUND: Hepatic stellate cells have been reported to play important roles in the regulation of hepatic microcirculation via cell contraction. Increase in intracellular calcium concentration is required to induce cell contraction. We have already reported the existence of L-type voltage-operated Ca2+ channels (VOCC), such as smooth muscle cells. On the other hand, alcohol has been known to disturb hepatic microcirculation. In this study, we evaluated the effect of acute and chronic treatment of alcohol on VOCC in rat hepatic stellate cells. METHODS: Stellate cells isolated from rats were cultured with or without 100 mM ethanol for up to 14 days. VOCC were detected by the patch clamp technique. Cells cultured for 14 days without ethanol were exposed to ethanol to investigate calcium current during membrane depolarization. alpha-Smooth muscle actin (alpha-SMA) was stained by indirect immunofluorescence. RESULTS: In the control model, VOCC were recognized in cells cultured for more than 7 days. Detection of VOCC increased from 9% on day 7 to 55% on day 14. On the other hand, VOCC in cells treated chronically with 100 mM ethanol appeared earlier than in the control and the incidences were significantly higher than those of the control accompanied with an early activation of cells. In contrast, simultaneous exposure to ethanol during the membrane depolarization inhibited Ca2+ current. CONCLUSIONS: The expression of Ca2+ channels in stellate cells were up-regulated by the chronic treatment of alcohol accompanied with the transformation to myofibroblast-like phenotype. However, alcohol itself inhibited Ca2+ current.