用荧光猝灭法研究人血清白蛋白与吲哚美辛的结合反应

应用荧光光谱法研究了吲哚美辛与人血清白蛋白(HSA)的相互作用. 发现吲哚美辛对HSA的荧光有较强的猝灭作用. 采用两种计算结合常数K^A的方法, 并对两种计算方法进行比较. 探讨了温度对吲哚美辛与HSA结合反应的影响, 得到了不同温度下的结合常数 K^A 与结合位点数n值. 进一步探讨了一些金属离子对吲哚美辛与HSA结合常数的影响. 根据热力学常数确定了它们之间的主要作用力类型.     

脑室微量注射兴奋性神经递质谷氨酸对消炎痛－胃溃疡的抑制效应

脑室微量注射兴奋性神经递质谷氨酸（Ｇｌｕ，１－７ｎｍｏｌ）可显著抑制小白鼠消炎痛－胃溃疡的发生（Ｐ＜０．０１），并呈现明显的剂量－效应依赖关系（ｒ＝－０．９３６，Ｐ＜０．０２）。腹腔注射Ｇｌｕ（１００ｎｍｏｌ）或尾静脉注射Ｇｌｕ（１００ｎｍｏｌ）对消炎痛－胃溃疡均无影响。胆碱能神经Ｍ受体阻断剂阿托品（ｓ．ｃ．０．０２ｍｇ·ｋｇ（－１））使溃疡明显加重，但它不能阻断Ｇｌｕ对消炎痛－胃溃疡的抑制效应。肾上腺素能神经α受体阻断剂酚妥拉明（ｉ．ｍ．２．５ｍｇ·ｋｇ（－１））对消炎痛－胃溃疡无影响，并且不能阻断Ｇｌｕ的抑制效应。以上结果提示，外源性Ｇｌｕ并非通过外周而是通过中枢特异性机制来抑制消炎痛－胃溃疡的。可能在消炎痛－胃溃疡发生中，边走神经紧张性活动对胃粘膜具有保护作用，而交感神经紧张性活动无作用。但Ｇｌｕ在中枢对消炎痛－胃溃疡的作用既不通过迷走神经，也不通过交感神经，而可能通过其它途径，如神经内分泌、血液循环等来抑制消炎痛－胃溃疡。     

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

These years Yuangong copper-bearing intrauterine devices （Cu-IUDs） have been used because of less side effects in use. The corrosion of copper is essential to the success of contraception, and the release behavior of indomethacin from medicated Cu-IUD is related to its therapeutic effect. In this study, analytical methods were established to investigate the release behavior of cupric ion of three kinds of Yuangong Cu-IUDs and indomethacin of medicated Yuangong 220 Cu-IUD. Cu-IUDs were incubated in simulated uterine solution （SUS）. The concentrations of cupric ion and indomethacin were analyzed by flame atomic absorption spectrometer （FAAS） for 60 days and UV/vis -3310 spectrophotometer for 60 days, respectively. The morphology of copper after corrosion was characterized by SEM. In addition, we detected cytotoxicity by MTT of L929 mouse fibroblasts cells caused by extracts of the three Yuangong Cu-IUDs. The release behavior of cupric ion for three kinds of Yuangong Cu-IUDs was biphasic, which consisted of the initial burst release and then slow and constant release. In vitro release experiment confirmed a biphasic release of indomethacin from Yuangong 220. The copper wire of Yuangong Cu-IUDs showed uneven corrosion. The RGR value of Yuangong 365 Cu-IUD was smaller than that of medicated Yuangong 220 Cu-IUD and RGR value of medicated Yuangong 220 Cu-IUD was smaller than that of Yuangong 300 Cu-IUD. The cupric ion release and indomethacin release showed biphasic. Indomethacin increased the cupric ion release rate and might diminish the adverse effects caused by burst release of cupric ion. The toxicity grade of these three Yuangong Cu-IUDs was 4. We should canvass the adverse events of Cu-lUDs based on practical experiments, and try our best to reduce the toxicity of Cu-lUDs.     

Inhibition of collagen synthesis by interleukin-1 in three-dimensional collagen lattice cultures of fibroblasts

Summary Interleukin-1 (II-1) was added to collagen lattice cultures of human skin fibroblasts. No cell division was induced, the ability of fibroblasts to contract the lattices was decreased and a dose-related inhibition of collagen synthesis without effect on non-collagen proteins was found. Indomethacin had no influence on these effects.     

Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

脑室注射GABA对小鼠实验性胃溃疡及其粘液屏障的影响

报道小白鼠脑室注射ＧＡＢＡ（４ｍｌ）对无水乙醇（０．ｌｍｌ灌胃）、盐酸（０．２Ｎ，０．２ｍｌ灌胃）、消炎痛（３２ｍｇ·ｋｇ－１肌肉注射）和冷束缚应激（１℃）四种不同实验性胃溃疡及其粘液屏障的影响。实验结果表明：乙醇、盐酸和冷束缚诱导胃溃疡时，胃壁粘液量都显著减少，而消炎痛则无变化。脑室注射ＧＡＢＡ能加剧乙醇诱导型、消炎痛诱导型这两种胃溃疡，但对胃壁粘液量无明显影响。而脑室注射ＧＡＢＡ能抑制盐酸诱导型、冷束缚应激型胃溃疡，并使固壁粘液明显升高。本文对中枢ＧＡＢＡ能机制参与胃溃疡及胃粘液调节作了进一步探讨。     

The possible involvement of protein kinase C and phospholipase A2 inHydra tentacle regeneration

The participation of protein kinase C (PKC) in the regeneration of tentacles ofHydra vulgaris was studied. Regeneration was induced by 1,2-sn-dioctanoyl-glycerol (diC₈) and the novel diterpenoidic diacylglycerol verrucosin B (VB), a potent PKC activator extracted from marine sources. VB substantially increasedHydra average tentacle number (ATN) at concentrations 10,000 times lower than those needed for diC₈ to exert an analogous effect. When both synthetic and natural VB analogues were tested, the structure/activity relationship found inHydra tentacle regeneration was identical to that known for DAG-induced activation of PKC in vitro. VB-induced increase of ATN was strongly counteracted by the PKC inhibitors sphingosine and A3, but was not synergic with a tenfold increase of extracellular Ca²⁺ concentration or with an increase of intracellular Ca²⁺ concentration obtained either with the ionophore A23187 or with thapsigargin. This suggested the involvement of a non-Ca²⁺-dependent PKC in VB-triggeredHydra tentacle regeneration. The involvement of phospholipase A₂ (PLA₂) activation inHydra regenerative processes was studied using the novel site-specific inhibitor of the enzyme, oleyloxyethylphosphorylcholine (OOPC), which brought about a striking inhibition of ATN in the low molar range. This effect was reversed by arachidonic acid (AA), while an enhancement of ATN was also observed with an inhibitor of AA uptake from membrane phospholipids, thus suggesting that PLA₂-catalysed liberation of AA is involved inHydra tentacle regeneration. OOPC also blocked verrucosin B-induced PKC-mediated enhancement of ATN, thus suggesting that this effect is also mediated by PLA₂ activation. ATN was increased also by compound 48/80, a direct activator of pertussis toxin-sensitive GTP-binding proteins, and this effect was counteracted by pertussis toxin pretreatment. None of the known AA cascade inhibitors exhibited an effect on ATN comparable to that exerted by OOPC, but, surprisingly, the cycloxygenase inhibitor indomethacin strongly enhanced ATN, thus suggesting that prostanoids might effect a negative control onHydra regenerative processes. This represents the first attempt so far reported to study the implication of more than one biochemical pathway as a signalling event in the hydroid regenerative processes.     

吲哚美辛对人喉癌Hep-2细胞系的抑制作用

目的：评价吲哚美辛对人喉癌Hep-2细胞系的抑制作用。方法：应用不同剂量的吲哚美辛作用于人喉癌细胞系Hep-2后，进行细胞形态观察，并用台盼蓝染色法检测细胞生长情况和流式细胞仪分析细胞DNA含量。结果：Hep-2细胞系在吲哚美辛作用下，细胞生长形态改变，细胞活力降低，流式细胞仪分析形成明显的亚二倍体峰，并与药物剂量及作用时间有依赖关系，电镜下见凋亡细胞。结论：吲哚美辛能抑制人喉癌细胞系Hep-2的生长，诱导细胞凋亡。     

再生丝素蛋白-壳聚糖包药微囊的质量研究

以模型药物消炎痛(吲哚美辛)作为芯料，在W／O型乳化体系中分别以复凝聚法制备再生丝素蛋白-壳聚糖包药微囊和以单凝聚法制备壳聚糖包药微囊，测试并分析了两种微囊的形貌、粒径、成囊率、包囊率和释药率等质量指标。结果表明，丝素-壳聚糖包药微囊的成囊率、包囊率比壳聚糖包药微囊高，药物缓释效果更好。     

胃复安增强大鼠胃肠肌电活动机制的探讨

给２０只Ｗｉｓｔａｒ大鼠胃窦和十二指肠浆膜面埋置不锈钢针形双极电极，以观察胃复安增强胃肠肌电活动的机制。结果发现：阻断胆碱能Ｍ受体后，胃复安增强胃窦肌电及十二指肠不规律锋电活动的作用消失；切除迷走神经后，胃复安对胃肠肌电活动的作用仍未消除；消炎痛可加强胃电高活动相，阻断胃复安对十二指肠规律锋电活动的加强作用，但对不规律锋活动的增强无影响。提示：胃复安增强胃窦肌电话动直接经外周胆碱能Ｍ受体发挥作用，