共查询到18条相似文献,搜索用时 203 毫秒
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苦参碱对脂多糖/痤疮丙酸杆菌诱导的小鼠肝炎及产生肿瘤坏死因子的影响 总被引:14,自引:0,他引:14
用小鼠致死性肝炎模型和TNF体外诱生的方法,研究苦参碱(Mat)对脂多糖(lipopolysaccharides,LPS)诱导的经痤疮丙酸杆菌(propionibacterittm acnes,PA)预刺激的小鼠产生肿瘤坏死因子(TNF)以及致死性肝炎的影响。结果表明:Mat(10,50mg·kg-1,ip,bid×3d)可降低血清TNF和ALT水平及小鼠对LPS致死毒性的敏感性,并可在体外抑制LPS诱导的经PA预刺激的小鼠腹腔巨噬细胞释放TNF。提示Mat的保肝作用与其抑制TNF释放有关。 相似文献
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为了寻找更有效的苯駢噻二嗉类的降压药物,合成了五个类型化合物共五十二个.(1)間位氯代苯胺与过量氯磺酸反应(另加三氯化磷),产生的双磺酰氯与氫氧化铵或脂族胺,芳香胺,脂环胺等作用可得到相应的双磺酰胺.間位三氟甲基苯胺先轉变成2-三氟甲基-4氨基-苯磺酸后再氯磺化、氨化可得到相应的双磺酰胺.苯胺經氯磺化、氨化得到三磺酰胺.(2)磺酰胺与脂族醛、芳香醛作用,縮合成苯駢噻二嗪类化合物.这些化合物不溶于水及酸而溶于碱,因此可利用此性质,进行化合物的純制.三磺酰胺与甲醛反应得到三环化合物,而与乙醛反应得苯駢噻二嗪衍生物.(3)双磺酰胺与酮也可进行縮合,但此醛类困难. 相似文献
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氧化苦参碱对BCG+LPS诱导小鼠免疫性肝损伤的保护作用 总被引:2,自引:1,他引:1
目的 观察氧化苦参碱(OM)对卡介苗(BCG)+脂多糖(LPS)诱导的BALB/c小鼠免疫性肝损伤后肝组织匀浆中一氧化氮(NO)、诱生型一氧化氮合酶(iNOS)、肿瘤坏死因子(TNF)、白介素1(IL-1)活性的影响.方法 除阴性对照组外,给予其余小鼠BCG+LPS诱导建立免疫性肝损伤小鼠模型,氧化苦参碱高、中、低剂量灌胃给药10d后,取肝组织匀浆,测定各组小鼠肝匀浆中的NO、iNOS及TNF、IL-1.结果 OM可明显降低肝匀浆中的NO、iNOS、TNF、IL-1含量(P<0.01).结论 OM对BALB/c小鼠免疫性肝损伤有明显的保护作用,保肝机制可能与其增强抗氧化活性有关. 相似文献
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蛋白激酶C激活剂和抑制剂对小鼠腹腔巨噬细胞释出肿瘤坏死因子的影响 总被引:8,自引:0,他引:8
本文研究蛋白激酶C(PKC)激活剂TPA和抑制剂H-7,槲皮素对痤疮丙酸杆菌(Propionibacterium acnes,PA)启动的小鼠腹腔巨噬细胞(macrophage,MΦ)释出肿瘤坏死因子(TNF)的影响,表明TPA可诱导PA启动的M分泌TNF,其作用可被H-7和槲皮素抑制,LPS体外和体内诱生TNF的作用亦可被两者抑制,提示PKC和PA启动的M分泌TNF过程中具有关键性作用。 相似文献
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α,ω-双-[对-氨基苯氧基]-烷类对感染日本血吸虫病的实驗动物具有显著疗效,惟毒性较大.本文叙述了α,ω-双-[对-甲氨基苯氧基]-戊烷及-庚烷-N,N′双取代衍生物的合成,希望这些衍生物的毒性减低,而疗效增大.n=5或7.R=-CH2SO·ONa,-CH2SO2·ONa,-CH2COONa, -CH2CONH2,-CH2CN,-CONH2,-COCH3,-CH2CONH2,-COOC2H5.N,N′-双甲亚磺酸鈉及N,N′-双甲磺酸鈉衍生物系以α,ω-双-[对-甲氨基苯氧基]-戊烷Ⅰ及庚烷Ⅱ分別与烴甲亚磺酸鈉及烴甲磺酸鈉在碱性甲醇中作用生成.N,N′-双甲磺酸鈉衍生物与氰化鉀反应得N,N′-双乙腈衍生物,再行水解則得N,N′-双乙酸鈉衍生物.由对-N-氨基碳酰甲基-N-甲氨基苯酚、对-N-氨基碳酰-N-甲氨基苯酚,以及对-N-β-羥乙基-N-甲氨基苯酚分別与α,ω-二溴烷类縮合,得N,N′-双乙酰胺、N,N′-双碳酰胺、以及N,N′-双-β-羥乙基衍生物.N,N′-双碳酰胺亦由Ⅰ及Ⅱ直接与氰酸鉀反应制得。N,N′-双甲酸乙酯衍生物系以Ⅱ与氯代甲酸乙酯作用合成,而N,N′-双乙酰衍生物則按常法制取之。 相似文献
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作者等用2-取代基-7,10-二氯苯骈[b]1,5-萘啶分别与取代氨基烃基胺和取代胺在苯酚中作用,合成了2-取代基-7-氯-10-(取代氨基烃基氨基)苯骈[b]1,5-萘啶(Ⅱ1~10,表1)和相应的10-(取代氨基)-苯骈[b]1,5-萘啶(Ⅱ11~14,表1);将2-取代基-7,10-二氯苯骈[b]1,5-萘啶与取代苯酚的钾盐作用,又合成了相应的10-(取代苯氧基)苯骈[b]1,5-萘啶(Ⅲ,表2)。在具有取代氨基烃基胺侧链的化合物中,以Ⅱ2,6,10对血液转种的Plasmodium berghei和子孢子诱发感染的P.yoelii两种鼠疟原虫的作用最显著;具有N-甲基-N′-氨基哌嗪侧链的Ⅱ11,经后一种鼠疟试验,也呈现了优于伯喹的显著的疗效;化合物Ⅲ1,3,4,7,8仅对后一种模型呈现较弱的作用。 相似文献
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氯萘磺酰胺类化合物的合成与蛋白激酶C免疫调节作用 总被引:1,自引:0,他引:1
为了研究蛋白激酶C抑制剂及激活剂对巨噬细胞释放肿瘤坏死因子的影响,作者设计并合成了十八个5-氯-1-萘磺酰胺类化合物,经初步药理试验表明,本类化合物中的抑制剂均能显著抑制TNF释放,而激活剂单独应用时不能引起TNF释放,但可增强内毒素引起的TNF释放。 相似文献
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The pectic polysaccharide, bupleuran 2IIb, up-regulates Fc-receptor (FcR) expression on peritoneal macrophages in a dose-dependent manner. The intracellular signal transduction by bupleuran 2IIb leading to the expression of FcR was studied. Neither the protein kinase C (PKC) inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride, nor the structurally distinct PKC antagonist, calphostin C, inhibited bupleuran 2IIb-induced up-regulation of FcR, whereas two direct activators of PKC, L-α-l-oleoyl-2-acetyl-sn-3-glycerol and N-(6-phenylhexyl)-5-chloro-l-naphthalenesulphonamide were unable to up-regulate the expression of FcR. The protein kinase A (PKA) inhibitor, N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide dihydrochloride also did not inhibit bupleuran 2IIb-induced up-regulation of FcR. Fluorescence image analysis using the calcium-sensitive dye, Fura-2, demonstrated that bupleuran 2IIb induced a rapid increase in intracellular levels of calcium (Ca2+). When macrophages were treated with calcium antagonist, 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride, bupleuran 2IIb-induced up-regulation of FcR was inhibited in a dose-dependent manner. The bupleuran 2IIb-induced up-regulation of FcR was also blocked by two structurally distinct calmodulin antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide hydrochloride. Furthermore, elevation of intracellular Ca2+ using the calcium ionophore, A23187, led to up-regulation of the FcR expression in a dose-dependent manner. These results suggest that bupleuran 2IIb induces the up-regulation of FcR on macrophages by a mechanism dependent on an increase in intracellular Ca2+ followed by activation of the calmodulin, but not by a PKC or PKA pathway. 相似文献
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蛋白激酶C激活剂和抑制剂对肿瘤坏死因子杀瘤活性的影响 总被引:2,自引:0,他引:2
以小鼠成纤维细胞瘤L929细胞为靶细胞,研究蛋白激酶C(PKC)的激活剂和抑制剂对人重组肿瘤坏死因子(rHuTNF)杀瘤活性的影响.各种药物与rHuTNF 10 ng·ml~(-1)和放线菌素D 1 μg·ml~(-1)温育18 h,结果表明PKC的激活剂佛波醇-12-肉豆蔻酸盐-13-乙酸盐(PMA)2.5~160ng·ml~(-1)可浓度依赖性地抑制rHuTNF的杀瘤活性.Sc-10(1~16μg·ml~(-1))单独作用很弱,但可浓度依赖地增强PMA 10 ng·ml~(-1)或A23187 0.5μg·ml~(-1)的抑制作用,PKC抑制剂1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)单独作用对rHuTNF杀瘤活性无影响,但可减弱PMA 50ng·ml~(-1)的抑制作用.槲皮囊2~16μg·ml~(-1)则可直接抑制rHuTNF的杀瘤活性,钙调蛋白抑制剂N-(6-氨己基)-5-氯-1-萘磺酰胺(W-7)及其同系物也有微弱的抑制作用.结果提示PKC在rHuTNF杀瘤作用中起着重要作用. 相似文献
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《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(7-8):593-602
1. N-(1′-Benzyl-4′-piperidyl-N-oxide)-4-amino-5-chloro-2-methoxybenzamide,N-(4′-(N-hydroxylpiperidyl))-4-amino-5-chloro-2-methoxybenzamide and N-(4′-(Δ1′-piperidyl-N-oxide))-4-amino-5-chloro-2-methoxybenzamide were obtained from chloro- form extracts of incubation mixtures of clebopride or desbenzyl clebopride with 9000g supernatant of liver homogenates of male NZW rabbits.2. These metabolites were identified using electron impact (low and high resolution) and field desorption mass spectrometry, and computer averaged time proton magnetic resonance spectroscopy. 相似文献
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Protein kinase C (PKC) is a Ca2+- and phospholipid-dependent protein kinase which has been implicated as a key enzyme in the regulation of cellular growth. The naphthalenesulfonamide W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] is representative of a number of cationic amphiphilic inhibitors of PKC which appear to inhibit PKC by interacting with the acidic phospholipid cofactor of the enzyme, according to kinetic studies. In a previous report, we demonstrated that PKC binds directly to W7 when the naphthalenesulfonamide is immobilized on agarose. In the present report, we have defined the mechanism of the binding of PKC to W7-agarose, and its relevance to the inhibitory mechanism of the naphthalenesulfonamide. We demonstrate that PKC bound W7-agarose through the catalytic domain of the enzyme. An active catalytic fragment of PKC was generated by limited proteolysis, and we found that this fragment bound W7-agarose and coeluted with intact PKC upon the addition of Triton X-100. W7 inhibited PKC activity by two different mechanisms. As previously reported, W7 inhibited PKC by interacting with the phospholipid cofactor of the enzyme (IC50 = 260 microM). However, at higher concentrations of W7, we found that this naphthalenesulfonamide inhibited PKC by serving as a competitive inhibitor with respect to the substrate ATP, according to a kinetic analysis of the inhibition of the active catalytic fragment of PKC by W7. W7 inhibited the active catalytic fragment of PKC as well as PKC-catalyzed phosphorylation of protamine sulfate, a reaction which is independent of Ca2+ and phospholipid, with similar potencies. Consistent with the kinetic evidence that W7 serves as a competitive inhibitor of PKC with respect to ATP, we found that, in the presence of 10 mM MgCl2, 1 mM ATP was sufficient to elute PKC from W7-agarose. Thus, naphthalenesulfonamide PKC inhibitors may include both agents which primarily function by interacting with the phospholipid cofactor of the enzyme and agents which primarily serve as active site inhibitors of PKC. 相似文献
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Inhibitory effects of calmodulin antagonists on isoproterenol- and dibutyryl cyclic AMP-stimulated amylase release from rat parotid acinar cells 总被引:1,自引:0,他引:1
The effects of three calmodulin antagonists on rat parotid amylase release were investigated in vitro using a dispersed acinar cell preparation. The potent calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), inhibited both 1 microM isoproterenol (ISO)- and 1 mM dibutyryl cyclic AMP (DBcAMP)-stimulated amylase release in a dose-dependent manner at concentrations of 25-100 microM. The IC50 values for the ISO-stimulated amylase release were 22 microM with TFP and 42 microM with W-7, and the values for the DBcAMP-stimulated release were 25 microM and 48 microM, respectively. The weak calmodulin antagonist, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), caused only slight inhibition at a concentration of 100 microM. These calmodulin antagonists only had a very small effect on the spontaneous release of lactate dehydrogenase. The results suggest that the calcium-calmodulin system may play a role in the exocytotic process of amylase release from the rat parotid gland. 相似文献
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