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白细胞介素⁃15预处理调控脓毒症诱导的心肌细胞凋亡及其相关机制研究
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作者 李惠 熊翅 +4 位作者 李浪 郭艳丹 张媛 王玉梅 许文平 《海军医学杂志》 2024年第7期683-689,共7页
目的研究白细胞介素(IL)⁃15对脂多糖(LPS)诱导的脓毒症心肌细胞凋亡的影响,并探讨其相关的作用机制。方法H9C2细胞分为对照组(常规培养的H9C2细胞)、凋亡组(建立LPS诱导的心肌细胞损伤模型,未进行其他干预)和干预组(采用10 ng/ml重组大... 目的研究白细胞介素(IL)⁃15对脂多糖(LPS)诱导的脓毒症心肌细胞凋亡的影响,并探讨其相关的作用机制。方法H9C2细胞分为对照组(常规培养的H9C2细胞)、凋亡组(建立LPS诱导的心肌细胞损伤模型,未进行其他干预)和干预组(采用10 ng/ml重组大鼠IL⁃15干预心肌H9C2细胞损伤模型6 h)。甲基噻唑基四唑(MTT)法和流式细胞仪检测IL⁃15干预对H9C2细胞增殖和凋亡的影响,四甲基罗丹明乙酯(TMRE)染色测定线粒体膜电位。10 mg/kg LPS腹腔注射建立小鼠脓毒症模型,采用腹腔注射含100μg/ml IL⁃15的生理盐水100μl进行干预。通过HE染色评估小鼠心肌病理损伤。ELISA法检测小鼠心肌组织氧化应激指标。实时荧光定量PCR和蛋白质印迹法检测小鼠心肌组织中血红素氧合酶(HO)⁃1、核转录相关因子2(Nrf2)mRNA和蛋白的表达。结果凋亡组H9C2细胞凋亡率[(47.9±5.1)%]明显高于对照组[(2.1±0.3)%],差异有统计学意义(P<0.05),而干预组H9C2细胞凋亡率[(20.7±2.7)%]则明显低于凋亡组(P<0.05)。LPS诱导可以显著抑制心肌细胞的增殖活性,IL⁃15能够抑制LPS诱导的心肌细胞活力降低(P<0.05)。凋亡组H9C2细胞线粒体膜电位相对值(2.6±4.6)明显低于对照组H9C2细胞线粒体膜电位相对值(7.4±5.2),差异有统计学意义(P<0.05);干预组H9C2细胞线粒体膜电位相对值(4.2±4.9)明显高于凋亡组(P<0.05)。LPS作用后显著增强了H9C2细胞线粒体膜电位的丧失,IL⁃15干预会减少LPS诱导的H9C2细胞线粒体膜电位的丧失。HE染色切片镜下观察显示小鼠脓毒症模型心肌组织出现明显损伤及炎症细胞浸润;IL⁃15干预可改善LPS诱导的小鼠心肌损伤。脓毒症模型小鼠心肌组织中超氧化物歧化酶(SOD)和总抗氧化能力(T⁃AOC)水平较正常小鼠明显降低,而丙二醛(MDA)水平则明显升高(P<0.05)。IL⁃15干预小鼠心肌组织SOD、T⁃AOC水平均升高,MDA水平均降低(P<0.05)。正常小鼠心肌组织中HO⁃1和Nrf2的mRNA和蛋白表达水平均较低;脓毒症模型小鼠心肌组织中HO⁃1、Nrf2的mRNA和蛋白表达水平较正常小鼠明显升高(P<0.05);IL⁃15干预小鼠心肌组织中HO⁃1、Nrf2的mRNA和蛋白表达水平进一步升高(P<0.05)。结论IL⁃15可减轻脓毒症诱导的心肌细胞凋亡,改善脓毒症小鼠心肌损伤程度。其机制可能与IL⁃15激活HO⁃1/Nrf2信号通路,进而抑制脓毒症心肌组织氧化应激有关。 展开更多
关键词 白细胞介素⁃15 脓毒症 心肌细胞凋亡 氧化应激
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Interleukin-15 Promotes the Commitment of Cord Blood CD34^+ Stem Cells into NK Cells
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作者 张建 夏青 +1 位作者 孙汭 田志刚 《Journal of Microbiology and Immunology》 2004年第1期40-44,共5页
To explore the effect of rhIL-15 on CB-CD34 + stem cells committing to NK cells, CD34 + stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expre... To explore the effect of rhIL-15 on CB-CD34 + stem cells committing to NK cells, CD34 + stem cells were obtained from cord blood (CB) by magnetic-assisted cell sorting (MACS) method. CD3, CD16 and CD56 molecules expressed on cell surface were detected by flow cytometer. MTT method was used to test the cytotoxicity of NK cells. The results were that stem cell factor (SCF) alone has no effect on CD34 + stem cells. IL-15 stimulated CD34 + stem cells commit to NK cells, and SCF showed strong synergistic effect with IL-15. It was concluded that IL-15 and SCF played different roles during NK cell development, IL-15 promoted CD34 + stem cells differentiate to NK cell precursor and SCF improved the effects of IL-15 on NK cell differentiation. 展开更多
关键词 IL-15 Differentiation NK cell Stem cell
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Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines 被引量:4
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作者 RuiSUN AiLingLI +1 位作者 HaiMingWEI ZhiGangTIAN 《Cell Research》 SCIE CAS CSCD 2004年第1期67-73,共7页
We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human N... We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation. 展开更多
关键词 prolactin receptor NK cell INTERLEUKIN-2 interleukin-15.
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