黄芩甙对发热大鼠下丘脑PGE2和cAMP含量的影响

目的和方法：PGE2和cAMP是重要的中枢发热介质。为了探讨PGE2和cAMP是否参与了黄芩甙解热的机制,本实验用内毒素（ET）复制大鼠发热模型,观察黄芩甙的解热作用及对大鼠下丘脑中PGE2和cAMP含量的影响。结果：黄芩甙有明显的解热作用,并且翻转ET对下丘脑中PGE2和cAMP含量的影响。相关分析显示,下丘脑中PGE2和cAMP含量的变化与体温变化之间存在明显正相关。结论：黄芩甙可通过抑制下丘脑中PGE2和cAMP含量升高而发挥其解热作用。     

α-黑色素细胞刺激素对白细胞介素-1β发热的解热机理研究

本研究观察了α－黑色素细胞刺激素（α－ＭＳＨ）对家兔白细胞介素－１β（ＩＬ－１β）发热效应及下丘脑组织腺苷环－磷酸（ｃＡＭＰ）含量的影响;同时观察了下丘本外培养过程中,α－ＭＳＨ对ＩＬ－１β刺激下丘脑释放ｃＡＭＰ的影响。结果显示：α－ＭＳＨ能显著降低ＩＬ－１β引起的体温升高（Ｐ〈０．０５）;同时抑制下丘脑组织ｃＡＭＰ含量的增高（Ｐ〈０．０１）。ＩＬ－１β与下丘脑组织培养,其上清液的ｃＡＭＰ含量明显     

地塞米松对TRAIL双向诱导猪肾成纤维细胞增殖与凋亡作用的影响

采用MTT掺入法检测细胞活率变化,分别筛选出诱导细胞增殖与凋亡的药物浓度;半定量PCR法检测不同浓度下地塞米松对骨保护素(Osteoprotegerin,OPG)和核因子κB受体激活剂受体配体(Ligand of receptor activator of nuclear factor kappa B,RANKL)基因在mRNA水平上的调控作用;流式细胞术检测细胞周期分布和凋亡率变化,显微镜观察FRSs存活、增殖和凋亡变化.经MTT检测和浓度筛选,发现TRAIL在0.01-5 mg/L浓度范围内诱导FRSs增殖,浓度增加到10 mg/L出现凋亡趋势.地塞米松可协同TRAIL双向诱导FRSs增殖或凋亡,有效浓度约10-6-10-10 mol/L.细胞周期分析与凋亡率检测结果表明RAIL诱导FRSs增殖峰浓度为5 mg/L.TRAIL(5 mg/L)与地塞米松协同作用,细胞增殖指数(Prl.)较TRAIL5 mg/L组上升2.49%(P<0.05);TRAIL 10 mg/L组与空白对照组比较细胞增殖指数和凋亡率无显著变化,TRAIL 10 mg/L与地塞米松协同作用G0/G1期比例较TRAIL10 mg/L组增加2.36%(P<0.05),凋亡率较之上升6.79%(P<0.01).地塞米松作用下,OPG基因mRNA水平表现下调,RANKL基因则表现上调,二者均表现为剂量依赖型.综上所述,TRAIL对FRSs呈诱导增殖或凋亡的双向调控作用,并呈剂量依赖型.地塞米松可协同TRAIL对FRSs作用,该现象与TRAIL和地塞米松诱导FRSs细胞周期的改变以及地塞米松对OPG/RANK/RANKL信号通路的OPG和RANKL基因的表达调控相关.     

壳聚糖-g-N.羧甲基-二(2-苯并眯唑)-1,2-乙二醇的制备及其性能

以2-溴乙酸、壳聚糖、二（2-苯并咪唑）-1,2-乙二醇为原料,利用接枝作用将化学修饰后的小分子药物二（2-苯并咪唑）-1,2-乙二醇连接在天然高分子壳聚糖（CTS）上。并以。HNMR,IR,热分析及XRD等方法对其结构进行表征并研究接枝聚合物的理化性质。本文采用络合滴定法测定了接枝聚合物对一系列重金属离子的吸附作用;采用震荡法进行悬菌定量杀菌实验;还以经典的静态失重法研究了合成的聚合物在腐蚀介质中对N80钢片腐蚀的抑制作用。结果表明：小分子药物-（2-苯并咪唑）-1,2-乙二醇在接枝到天然高分子壳聚糖后热稳定性提高,在酸中具有良好的溶解度,对金属离子吸附能力在一个较宽温度范围内得以保持;同时增强了抑菌力,降低了最小抑菌浓度;利用BBIE与CTS韵协同作用提高了聚合物对金属腐蚀的抑制能力。     

口服利尿药的研究——Ⅱ.5-氯-2,4-双磺酰氨基-苯胺(DSA)的利尿作用和体內代謝

本研究系比较CT与其水解产物——DSA对大鼠的利尿作用并探讨DSA在大鼠体内的转化、吸收、分布和排泄。大鼠口服20及100毫克/公斤时DSA的利尿及排氯作用与CT相同,口服CT或DSA 4毫克/公斤后,则作用均不明显。水解前后比色或纸层分析都证明服药后的大鼠尿中没有DSA的乙酰化产物或其他代谢产物。口服DSA 20毫克/公斤后,药物被迅速吸收,1、3、9小时的胃腸道含药量分别为口服剂量的55、20及12％。大鼠口服DSA 4—100毫克/公斤后,3小时内自尿排出剂量的30％左右,口服CT4毫克/公斤后同时期内排出剂量的34％,但加大剂量到20及100毫克/公斤时,仅排出剂量的17—18％。反之,静脉注射20毫克/公斤后,CT自尿排出比DSA迅速。自胆汁排出的药量少于口服剂量的1％。大鼠口服DSA 20毫克/公斤后1小时,药物在肾脏分布最多,肝次之。但总的说来,本药在各脏的浓度较趋平均。     

15甲-前列腺素F_(2α)对家兔子宫收缩及血浆孕酮水平的影响

本文报道 15甲-前列腺素PG F_(2α)对家兔子宫收缩及血浆孕酮水平的影响。15甲-PGF_(2α)0.4mg/kg、0.2mg/kg 对大鼠抗早孕均有明显作用,能使蜕膜细胞变性,胎盘剥离。15甲-PGF_(2α)剂量为0.4mg/kg时,对家兔在位子宫内压及收缩频率有显著的加强作用。15甲-PGF_(2α)剂量为0.4mg/kg时,对妊娠家兔有明显的降低血浆孕酮作用。     

(2E,4 E)-N-(2-氨基乙基-5-(苯并[d][1,3][二氧杂环戊烯]-5基)戊-2,4-二烯酰胺的合成及其降血脂作用

以金属钠为催化剂,加热回流合成(2E,4E)-N-(2-氨基乙基-5-(苯并[d][1. 3][二氧杂环戊烯]-5基)戊-2,4-二烯酰胺(C14H16N2O3,胡椒酸乙二胺,EPA),利用XRD、IR、1H、13C NMR对产物结构进行了表征和确认。以EPA的产率为指标,研究其最佳合成工艺参数。实验结果表明:当催化剂用量为1. 0 g(通氮气保护),加热回流温度65~70oC,反应时间45~48 h,为较好的合成工艺条件,EPA的合成收率达62. 93%以上,论文研究结果可为工业化生产提供设计依据。同时,EPA能显著降低高脂血症大鼠的血清TC、TG和LDL-C水平,且呈剂量依赖性; 2. 5 mg/kg剂量时显著升高HDL-C水平;并能显著升高高脂血症大鼠血清SOD和GSH-PX活力降低MDA含量。由此可知,降血脂作用与传统降血脂药物辛伐他汀相比,以降LDL-C作用更为明显。EPA具有一定的辅助降血脂功能及抗氧化作用。     

山莨菪碱(654-2)抗体休克作用机制的研究进展

六十年代至七十年代前期,从临床观察及部分实验材料认为654-2的抗休克作用主要是通过其扩血管作用改善微循环。七十年代后期以未,大量实验研究结果说明,654-2抗休克作用的机制主要不是通过扩张血管增加器官血流量,而在于它能在细胞水平上保护细胞、提高细胞对缺血缺氧的耐受性,从而稳定溶酶体和线粒体等亚细胞结构,减少溶酶体酶的释放和休克因子的产生,因而减轻或防止休克过程向不可逆发展的倾向。     

3,6-(二甲氨基)-二苯并碘杂六环葡萄糖酸盐对损伤心肌细胞的保护作用

目的：观察3,6-（二甲氨基）-二苯并碘杂六环葡萄糖酸盐（IHC-93）对培养心肌细胞损伤的影响。方法：在培养的心肌细胞建立低氧／复氧损伤模型和过氧化氢损伤模型,观察心肌细胞存活率、乳酸脱氢酶（LDH活性、超氧化物歧化酶（SOD）活性、丙二醛（MDA含量,以研究IHC-93对培养心肌细胞损伤的影响。结果：10、20、40μmol／LIHC-93呈剂量依赖地提高损伤心肌细胞存活率和SOD的活性,减少LDH的释放,降低MDA含量。结论：IHC-93对损伤心肌细胞具有直接保护作用。     

ZnCl2对月季切花的保鲜作用(简报)

用不同浓度ZnCl2溶液处理月季切花,以0.01%浓度保鲜效果最好,能延长切花瓶插寿命3d;同时,ZnCl2处理可使月季切花花枝硬挺,提高观赏价值。     

ANTIPYRETIC ACTION OF DEXAMETHASONE ON EGTAZIC ACIDINDUCED FEVER IN RABBITS

本文用脑室灌注和Ｆｕｒａ２测定细胞内游离钙技术观察了地塞米松（ｄｅｘａｍｅｔｈａｓｏｎｅ,ＤＥＸ）对家兔乙二醇双（２氨基乙醚）四乙酸性发热效应和下丘脑细胞内游离钙浓度（［Ｃａ２＋］ｉ）的影响,借此深入探讨地塞米松解热作用的中枢机制。结果发现：脑室灌注乙二醇双（２氨基乙醚）四乙酸（０６ｎｍｏｌ）引起家兔结肠温度明显升高,静脉注射地塞米松（５ｍｇ／ｋｇ）显著抑制家兔乙二醇双（２氨基乙醚）四乙酸性发热,地塞米松（６０～１２０μｍｏｌ／Ｌ）并不影响下丘脑细胞内［Ｃａ２＋］ｉ,而事先脑室灌注抑制基因转录的放线菌素Ｄ（３ｎｍｏｌ）则完全取消了地塞米松对乙二醇双（２氨基乙醚）四乙酸性发热的解热作用。这些结果提示：地塞米松显著抑制家兔乙二醇双（２氨基乙醚）四乙酸性发热,其机制与地塞米松激活脑内某些基因的表达有关,而与下丘脑神经细胞跨膜钙离子流无关。     

Stimulation of transcriptional expression of human UDP-glucuronosyltransferase 1A1 by dexamethasone

Human UDP-glucuronosyltransferase (UGT) 1A1 is only enzyme in the conjugation of bilirubin for prevention of hyperbilirubinemia and jaundice. Deletion or mutation of the UGT1A1 gene causes Crigler-Najjar syndrome or Gilbert's syndrome. We previously reported the functional promoter region for expression of UGT1A1 [Hepatology Research 9, 152-163 (1997)]. We investigated the influence of some drugs on the transient transfection assay of the luciferase reporter gene containing the 5'-promoter region -3174/+14 of UGT1A1 in HepG2 cells. Among drugs investigated, dexamethasone was the most effective at the range of concentration of 10-100 microM, whereas stimulation by beta-estradiol was not found. We also could not find stimulation by bilirubin of the endogenous main substrate for UGT1A1. Stimulation by dexamethasone was continued for 48 hr. The luciferase reporter gene containing the 5'-region of -97/+14 was induced by dexamethasone but the gene of the 5'-region -53/+14 was not. The region -97/-53 is essential for induction by dexamethasone. This region contains HNF1 element, therefore, we speculated that dexamethasone directly and/or indirectly stimulates UGT1A1 expression through this HNF1 region in the promoter region of UGT1A1. Thus, we clarified that UGT1A1 was induced by dexamethasone and the key position was the region (-97/-53) in UGT1A1 promoter.     

Suppression of protein kinase C and the stimulation of glucocorticoid receptor synthesis by dexamethasone in human fibroblasts derived from tumor tissue

Exposure of fibroblasts derived from keloid tissues, desmoid and dermal tissue from individuals with Gardner's syndrome (GS) to dexamethasone resulted in the suppression of protein kinase C (PKC) activity and [3H]thymidine incorporation into DNA, and a 20-fold induction of glutamine synthetase activity. Treatment of GS and keloid fibroblasts with 0.1 microM dexamethasone for 36 h increased glucocorticoid receptor (GR) synthesis, as determined by [35S]methionine labeling and immunoprecipitation with a monoclonal antibody to the human GR. The suppression of PKC activity by dexamethasone was shown to result from a loss of protein mass as determined by immunoblotting using an antibody to PKC type III. In contrast to these results, exposure of fibroblasts isolated from normal tissues to dexamethasone did not result in the suppression PKC and [3H]thymidine incorporation, there was only a sixfold induction of glutamine synthetase, and a decrease of GR synthesis. As no primary receptor binding defect could be detected, the altered response of tumor cells to steroid-occupied receptor indicates a partial post-receptor binding defect in GS and keloid cells.     

Cortisone and dexamethasone inhibit myogenesis by modulating the AKT/mTOR signaling pathway in C2C12

Myogenesis occurs in both the prenatal and postnatal periods and the prenatal myogenesis is related to the postnatal myogenesis and the incidence of disease later in life. Glucocorticoids used as therapeutic agents for many diseases, but cause adverse effects on muscle homeostasis, including defects in fetal muscle development. The action of glucocorticoids on differentiated skeletal muscle was well studied, but their effects on myotube formation have not been well investigated. Dexamethasone (DEX) and cortisone (COR), two synthetic therapeutic glucocorticoids, suppress myotube formation in C2C12 cells. Both COR and DEX attenuated myotube formation through modulation of myogenic regulatory factors. In addition, they affected the IGF/PI3K/AKT/mTOR signaling pathway, resulting in increased proteolytic protein (atrogin-1 and MURF1) for muscle degradation and decreased ribosomal S6 phosphorylation. The current results conclude that COR and DEX inhibit myotube formation in C2C12 cells by modulating both the myogenic program via MRFs and protein metabolism via IGF/PI3K/AKT/mTOR signaling pathway.     

Differential regulation by dexamethasone of glucocorticoid receptor messenger RNA concentrations in neuronal cultures derived from fetal rat hypothalamus and cerebral cortex

1. Differential regulation, by dexamethasone, of glucocorticoid receptor gene expression was studied in three different neuronal cultures derived from hypothalamus amygdala, and cerebral cortex. 2. Cellular glucocorticoid receptor (GR) mRNA concentration was measured by hybridization using a 32P-labeled RNA probe complementary to a 2.2-kb fragment of the glucocorticoid receptor mRNA. Changes in the amount of GR mRNA were evaluated in relation to the content of beta-actin mRNA. 3. In cells derived from either hypothalamus or cerebral cortex, we observed a complex pattern of GR mRNA concentrations which were characterized by cyclic variations of GR mRNA content during continuous treatment with dexamethasone for up to 72 hr. 4. In contrast to cells derived from the hypothalamus where a persistent 30-40% reduction in GR mRNA levels was seen for up to a least 72 hr, we observed, in cells derived from the cerebral cortex, a sustained increased (1.4-fold) of the GR mRNA at this same time interval.     

Dexamethasone induces the secretion of annexin I in immature lymphoblastic cells by a calcium-dependent mechanism

The mechanisms by which glucocorticoids (GC) regulate annexin I (ANXA1) secretion in different cells are still a matter of debate. The aims of this study were to evaluate the ability of dexamethasone (Dex) to induce ANXA1 secretion and to investigate the roles of the intracellular free Ca²⁺ concentration ([Ca²⁺]_i), and of the GC receptor, on that process. For this purpose, the human immature lymphoblastic CCRF-CEM cell line was used. Treatment of the cells with Dex, for up to 4 h, significantly reduced the intracellular content of ANXA1 and increased the amount of this protein bound to the outer surface of the plasma membrane, whereas exposure of cells to Dex, for 12 h, induced the synthesis of ANXA1. At the same short time periods, Dex also induced a significant increase in the [Ca²⁺]_i. Incubation of the cells with BAPTA-AM (10 M), a cell-permeant high affinity Ca²⁺ chelator, completely inhibited Dex-induced ANXA1 secretion. Furthermore, the Ca²⁺ ionophore, ionomycin, alone induced ANXA1 cleavage, but not its secretion. Additionally, we used brefeldin A to investigate the involvement of the classical endoplasmic reticulum (ER)-Golgi pathway of protein secretion in the release of ANXA1. The GC receptor antagonist, RU486, neither reverted the Dex-dependent ANXA1 secretion nor inhibited the increase of the [Ca²⁺]_i induced by Dex. Together, our results indicate that Dex induces ANXA1 synthesis and secretion in CCRF-CEM cells. ANXA1 secretion in this cell type show the following characteristics: (i) is unlikely to involve the classical ER-Golgi pathway; (ii) requires a Ca²⁺-dependent cleavage of ANXA1; (iii) involves both Ca²⁺-dependent and independent mechanisms; and (iv) is apparently independent of the GC receptor alpha isoform.     

黄热病现状及其疫苗的研究与应用

黄热病(yellow fever,YF)是一种经由伊蚊叮咬传播的急性出血性传染病,流行区主要集中在非洲西部、南美洲等热带地区,临床症状包括高热、恶心、呕吐、黄疸、出血等。黄热病的病原体为黄热病毒(yellow fever virus, YFV),是黄病毒科黄病毒属的单股正链RNA病毒。目前,YF治疗尚无特效药物,以对症治疗和支持治疗为主,接种YF-17D减毒活疫苗是最有效的预防方法。尽管YF-17D已被全球认可,但是疫苗接种所致的不良反应时有报道。本文对近年黄热病的流行情况、疫苗研究进展和应用进行综述。