白细胞介素－1对粒系细胞和红系细胞的正负调节作用

应用重组人白细胞介素－１β（γｈＩＬ－１β）对小鼠骨髓和外周血粒系细胞与红系细胞作用的研究表明：ＩＬ－１单剂量腹腔注射后ｄ７红系造血细胞明显减少，网织红细胞在ｄ８显著下降。５～１０万Ｕ·ｋｇ－１剂量范围内ＩＬ－１促进粒系细胞的增殖和分化成熟。应用流式细胞仪对骨髓细胞周期分析显示骨髓大体积细胞在注射ＩＬ－１后ｄ３Ｓ期细胞明显增多。我们的结果表明ＩＬ－１抑制红系造血细胞的分化增殖，在适当的剂量范围内促进粒系细胞的增殖和分化成熟。其作用的分子基础是诱导造血细胞的细胞周期变化。     

白细胞介素－1对粒系细胞和红系细胞的正负调节作用

应用重组人白细胞介素－１β（γｈＩＬ－１β）对小鼠骨髓和外周血粒系细胞与红系细胞作用的研究表明：ＩＬ－１单剂量腹腔注射后ｄ７红系造血细胞明显减少，网织红细胞在ｄ８显著下降。５～１０万Ｕ·ｋｇ－１剂量范围内ＩＬ－１促进粒系细胞的增殖和分化成熟。应用流式细胞仪对骨髓细胞周期分析显示骨髓大体积细胞在注射ＩＬ－１后ｄ３Ｓ期细胞明显增多。我们的结果表明ＩＬ－１抑制红系造血细胞的分化增殖，在适当的剂量范围内促进粒系细胞的增殖和分化成熟。其作用的分子基础是诱导造血细胞的细胞周期变化。     

重组人白介素1α引起小鼠骨髓基质细胞膜超极化

重组人白介素１α引起小鼠骨髓基质细胞膜超极化１吴曙光肖学军徐伟鲍永耀（第一军医大学药物研究所，广州５１０５１５）白介素１（ｉｎｔｅｒｌｅｕｋｉｎ－１，ＩＬ－１）是具有广泛生物学活性的多肽，其生物活性通过受体介导［１］，但至今有关ＩＬ－１与受体结合后的...     

吲哚美辛对脂多糖引起的人类风湿性关节炎滑膜细胞中白介素-6表达的影响

目的研究吲哚美辛对脂多糖引起的人类风湿性关节炎（RA）成纤维状滑膜细胞(FLS)中白介素-6（IL-6）表达的影响。方法用放免分析法检测IL-6蛋白的表达水平； RT-PCR方法测定IL-6 mRNA的表达水平。结果LPS处理对FLS中IL-6表达无显著影响； LPS刺激的U937细胞培养液上清液可明显增强FLS 中IL-6蛋白分泌及mRNA表达； 吲哚美辛可显著抑制上述变化，且其抑制作用随浓度的增加而增强。结论吲哚美辛可抑制LPS刺激的U937细胞培养上清液引起的FLS中IL-6的表达。     

Sodium perbarate and benzalkonium chloride induce DNA damage in Chang conjunctival epithelial cells

Content and objective: To investigate and compare the toxic effects of benzalkonium chloride (BAC) and new type oxidative preservative sodium perborate (NaBO₃) on DNA damage, reactive oxygen species (ROS), and cell survival in immortalized human Chang conjunctival cells.

Materials and methods: Cells were exposed to BAC and NaBO₃ in concentrations of 0.00001–0.001% for 30?min. Cell viability was measured by the MTT test. Alkaline comet assay was used to detect DNA damage. Mitochondrial membrane potential (MMP), cell apoptosis, and ROS production were detected by flow cytometry analysis.

Results: Significant changes in the relative cell survival rate in cells were observed after exposure to 0.0005–0.001% BAC for 30?min (p?p?3 did not induce the decrease in cell survival and MMP in low concentration but could induce DNA damage and ROS generation in a 0.001% concentration (p?Discussion and conclusions: BAC can induce DNA damage in human conjunctival epithelial cells; this effect may be related to oxidative stress. Although NaBO₃ did not induce a significant decrease in cell survival and MMP, DNA damage and ROS generation were still detected in high concentration. New type oxidative preservative has less toxicity than the old type, but it still has the tendency of producing genotoxic changes in an in vitro test system.     

白细胞介素-1、8在门脉高压症中的作用

目的：探讨白细胞介素－1、8在门脉高压症中的作用。方法：放免分析法测定白细胞介素－1、8含量。结果：白细胞介素－1、8与一氧化氮合成酶（NOS）、谷丙转氨酶（ALT）、谷草转氨酶（AST）有高度相关性。结论：白细胞介素－1、8参与高动力循环综合征（HCS）并与肝功能的损害有一定的关系。     

白细胞介素—1阻滞剂CK—119和CK—122地成纤维样细胞增生的抑制

AIM: To study potent and nontoxic agents to inhibit fibroblast proliferation. METHODS: Fibroblast-like corneal and conjunctival cells were cultured and inhibited by interleukin-1 (IL-1) blockers, dihydropyridazino-pyridazines CK-119 and CK-122. The cell growth and syntheses of DNA, RNA, and protein after IL-1 blocker incubation were determined. RESULTS: CK-119 and CK-122 inhibited cell growth of corneal fibroblast at 30 mg.L-1. DNA and RNA syntheses in corneal fibroblasts were markedly inhibited by CK-119 and CK-122 whereas protein synthesis was either unaffected or mostly enhanced at 30-100 mg.L-1 and 100-300 mg.L-1, respectively. Similar results were obtained in conjunctival cell cultures by CK-119 and CK-122 at 3-10 mg.L-1 and 30-100 mg.L-1, respectively. CONCLUSION: CK-119 and CK-122 are potent IL-1 blockers to inhibit cell growth of fibroblast-like corneal and conjunctival cells mainly through the inhibition of DNA and RNA syntheses but not protein synthesis.     

脂多糖对人类风湿性关节炎滑膜细胞白介素-6表达的影响脂多糖对人类风湿性关节炎滑膜细胞白介素-6表达的影响

目的研究脂多糖（LPS）及其刺激的U937细胞培养上清液和地塞米松对人类风湿性关节炎（RA）成纤维状滑膜细胞(FLS)白介素-6（IL-6）表达的影响。方法用放免分析法检测IL-6蛋白的表达；RT-PCR法测定IL-6 mRNA的表达。结果LPS处理对FLS中IL-6表达无显著影响；LPS刺激的U937细胞培养上清液可明显增强FLS中IL-6蛋白分泌及mRNA表达；地塞米松可显著抑制上述变化，且其抑制作用随浓度的增加而增强。结论LPS刺激的U937细胞上清液使FLS中IL-6表达增加；而地塞米松能抑制上述IL-6的变化。     

金雀异黄素对IL-1α刺激破骨样细胞的组织蛋白酶K表达的影响

目的探讨金雀异黄素对白细胞介素1α(IL-1α)刺激破骨样细胞组织蛋白酶K(CK)表达的作用.方法从人骨巨细胞瘤组织中纯化出破骨样细胞(OCLs),用不同浓度的金雀异黄素或1 7β-雌二醇(17β-E2)孵育,并设空白对照组和阳性对照组,采用RT-PCR和Western blot方法,观察IL-1α刺激后CK的表达.结果与空白对照组相比,IL-1α刺激CK表达显著增加(P＜0.01);金雀异黄素在转录水平下调IL-1α刺激后CK的表达,且呈剂量依赖关系(r=0.68,P＜0.01);金雀异黄素下调IL-1α刺激后CK的蛋白表达,且呈剂量依赖关系(r=0.61,P＜0.01).雌激素受体拮抗剂ICI 182.780可以部分抑制金雀异黄素的上述作用.结论金雀异黄素可通过破骨样细胞的雌激素受体部分抑制IL-1α刺激后CK的表达.     

西替利嗪干预组胺诱导的真皮成纤维细胞IL-8和MCP-1产生

目的　探讨真皮成纤维细胞组胺H1 受体(histamineH1 receptor,H1R)表达及西替利嗪(cetirizine,CET)对组胺(histamine,HIS)诱导炎症因子的干预作用,寻找CET抗皮肤过敏炎症的作用靶点。方法　采用RT- PCR和免疫组化技术检测真皮成纤维细胞H1RmRNA和蛋白表达;用HIS处理细胞为模型组,ELISA检测HIS诱导IL 8和MCP -1的蛋白分泌及CET的干预作用。结果　真皮成纤维细胞有H1RmRNA和蛋白表达; 10-6 ~10-4 mol·L-1 HIS显著地诱导了真皮成纤维细胞IL -8蛋白分泌(P<0 .05vs对照组),10-5 mol·L-1 HIS明显地诱导了MCP 1分泌(P<0 .01vs对照组),加入10-6、10-5 mol·L-1 CET共同培养24h,抑制了HIS诱导的IL- 8和MCP -1表达(P<0 .05vs模型组)。结论　CET可能通过抑制真皮成纤维细胞趋化因子的表达而发挥抗皮肤过敏炎症作用。     

Decreased viability and proliferation of CHANG conjunctival epithelial cells after contact with ultraviolet light-irradiated pollen

Context: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase.

Objective: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells.

Materials and methods: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system.

Results: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen.

Discussion and conclusions: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.     

Inhibition of fibroblast-like cell proliferation by interleukin-1 blockers, CK-119 and CK-122

Ｉｎｈｉｂｉｔｉｏｎｏｆｆｉｂｒｏｂｌａｓｔｌｉｋｅｃｅｌｐｒｏｌｉｆｅｒａｔｉｏｎｂｙｉｎｔｅｒｌｅｕｋｉｎ１ｂｌｏｃｋｅｒｓ，ＣＫ１１９ａｎｄＣＫ１２２ＢｏＸＵＡＮ，ＧｅｏｒｇｅＣＹＣＨＩＯＵ１（ＩｎｓｔｉｔｕｔｅｏｆＯｃｕｌａｒＰｈａｒ...     

氯通道阻滞剂NPPB对人肾小球系膜细胞增殖的抑制作用氯通道阻滞剂NPPB对人肾小球系膜细胞增殖的抑制作用

目的研究氯通道阻滞剂5-硝基-2-(3-苯丙胺)苯甲酸［5-nitro-2-(3-phenylpropylamino)- benzoic acid，NPPB］对肾小球系膜细胞增殖的作用及可能的机制。方法细胞计数和³H-TdR参入量测定确定细胞增殖，应用流式细胞术检测细胞周期时相。结果与对照组相比，氯通道阻滞剂NPPB和细胞外高渗透压力使人肾小球系膜细胞数和³H-TdR参入量明显减少，并呈剂量依赖关系,但不增加系膜细胞乳酸脱氢酶释放量。NPPB使细胞周期停滞在G0/G₁期。结论氯通道阻滞剂NPPB对人肾小球系膜细胞增殖有抑制作用,其机制与细胞容量改变有关。     

芒果苷衍生物的合成及其PTP1B酶抑制活性研究

目的设计合成一系列芒果苷衍生物并进行体外蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性实验。方法利用亲核取代反应在芒果苷上引入疏水苄基,设计合成8个新化合物4~11,采用比色法对化合物进行PTP1B抑制活性研究。结果设计合成的8个化合物对PTP1B酶都有一定的抑制作用。结论芒果苷衍生物的活性明显好于芒果苷本身的活性,苄基的对位取代活性要优于邻位和间位取代,且苄基上氯原子取代的衍生物要高于其它原子取代的化合物活性。     

Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis

Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed that PPF at concentrations ranging from 0.0625 to 1.0?g/l had poignant cytotoxicity to HCE cells, and the extent of its cytotoxicity was dose- and time-dependent. Further characterization indicated that PPF induced plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. In conclusion, PPF above 0.0625?g/l has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic.     

尕代类风湿关节炎成纤维样滑膜细胞及成熟细胞系生长特性的比较

目的通过对原代类风湿关节炎成纤维样滑膜细胞及成熟细胞系生长特性进行比较,为类风湿关节炎（RA）研究用细胞提供多重选择。方法分离培养原代类风湿关节炎成纤维样滑膜细胞,传至第三代,与成熟细胞系镜下观察细胞形态。此外,以相同细胞数接种,观察细胞增殖速度。结果形态上原代类风湿关节炎成纤维样滑膜细胞与成熟细胞系有所差别,且增殖速度细胞系快于原代细胞。结论成熟细胞系可在一定程度上反映原代细胞的状态,并用于RA相关疾病研究。     

Effect of aphidicolin on DNA synthesis in HSV-1 infected and uninfected Vero cells

The effect of aphidicolin on DNA synthesis in herpes simplex virus type 1 (HSV-1) infected and uninfected Vero cells was determined by isodensity banding of [³²P]-labelled DNA. A 50% inhibition of HSV-1 DNA synthesis was observed at 0.07 μM aphidicolin while 2.1 and 1.3 μM were required to inhibit the cellular DNA synthesis to 50% in infected and uninfected Vero cells, respectively. When the viral DNA synthesis was totally inhibited by 10 μM aphidicolin, the cellular DNA synthesis was inhibited to about 90% in both infected and uninfected cells. Aphidicolin inhibited the cellular DNA synthesis in HSV-1 infected and uninfected Vero cells remaining in the presence of 250 μM foscarnet to the same extent as the DNA synthesis in the absence of foscarnet.     

聚乙二醇修饰聚酰胺-胺的合成、表征及其人角膜上皮细胞毒性

目的:研究不同相对分子质量聚乙二醇(PEG)修饰不同代数树枝状大分子聚酰胺-胺(PAM-AM)得到的产物,测定其对人体角膜上皮细胞(HCECs)的毒性。方法:采用硝基苯氯甲酸酯(p-NPC)将单甲氧基聚乙二醇(mPEG,相对分子质量为750,2 000,5 000)活化成PEG碳酸酯,对第4,5代PAMAM大分子进行修饰;目标产物用FT-IR、1H-NMR进行结构表征;采用WST-8法考察PEG修饰对PAMAM的人角膜上皮细胞(HCECs)毒性的影响。结果:PAMAM经较低浓度PEG修饰后,对HCECs的毒性减弱不明显,经较高浓度PEG修饰后,对HCECs减毒明显减弱,不同相对分子质量的PEG修饰对PAMAM的减毒作用无明显差异。结论:经PEG修饰后,可以降低PAMAM对HCECs的毒性,作为新型眼部给药载体具有良好的前景。     

Effects of Ca channel blockers on Ca loading induced by metabolic inhibition and hyperkalemia in cardiomyocytes

The effects of the L-type (nifedipine and verapamil) and the T-type (mibefradil) Ca²⁺ channel blockers on the increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) induced by NaCN metabolic inhibition and hyperkalemia were examined in chicken cardiomyocytes using fluorescence imaging with Fura-2. NaCN induced a slow and sustained rise in [Ca²⁺]_i, which was not affected by pretreating the cells for 5 min with nifedipine, verapamil, or mibefradil at 100 nM or 10 μM. Pretreatment of the cells with 10 μM nifedipine, verapamil, or mibefradil for 5 min remarkably inhibited the K⁺-induced increase in [Ca²⁺]_i. These inhibitory effects diminished after 48-h pretreatment with nifedipine or verapamil but not with mibefradil. Ryanodine also induces an increase in [Ca²⁺]_i, and this effect was enhanced by 48-h pretreatment of the cells with 10 μM verapamil but not with 10 μM mibefradil. We conclude that the NaCN-induced increase in [Ca²⁺]_i is independent of the Ca²⁺ influx though the L-type or T-type Ca²⁺ channels. Chronic inhibition of the L-type Ca²⁺ channels but not T-type channels may enhance the ryanodine receptor-mediated Ca²⁺ release, which may be responsible for the development of tolerance to their inhibitory effects on K⁺-induced increase in [Ca²⁺]_i.