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超声介导携氧载紫杉醇脂质微泡抑制乏氧巨噬细胞HIF-1α表达

Ultrasound-mediated oxygen and paclitaxel loaded liposome microbubbles inhibits HIF-1α expression in hypoxic macrophages
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摘要 目的探讨超声介导携氧载紫杉醇脂质微泡对乏氧巨噬细胞HIF-1α表达的影响。方法 CoCl_2化学诱导小鼠巨噬细胞RAW264.7乏氧模型,将乏氧巨噬细胞分成6组(n=13):对照组、紫杉醇组(6×10^(-6)mol/L)、超声组(0.5 W/cm^2,30 s)、携氧微泡组(25μL)、携氧载紫杉醇脂质微泡组(25μL)和超声介导携氧载紫杉醇脂质微泡组(25μL;0.5 W/cm^2,30 s)。MTT测定巨噬细胞活性、RT-PCR和Western blot检测各组干预后HIF-1α的表达,ELISA试剂盒测定干预后上清液TNF-α和IL-6的含量。结果 CoCl_2100μmol/L作用12 h细胞活性抑制率低于8%,可成功诱导乏氧状态;超声介导携氧载紫杉醇脂质微泡抑制乏氧巨噬细胞HIF-1α基因和蛋白的表达并抑制TNF-α和IL-6的分泌(P<0.05)。结论超声介导携氧载紫杉醇脂质微泡能抑制乏氧巨噬细胞HIF-1α表达,从而改善其乏氧状态。 Objective To determine the effect of oxygen and paclitaxel loaded liposome microbubbles mediated by ultrasound on the expression of HIF-1α in hypoxia macrophages. Methods Hypoxia model of macrophages RAW264.7 was induced by COC12. Hypoxic RAW264.7 cells were randomly divided into control, paclitaxel group （6 × 10-6 mob/L）, ultrasound group （0.5 W/cm2, 30 s）, oxygen loaded liposome microbubbles （25 μL）, oxygen and paclitaxel loaded liposome microbubbles group （25 μL）, oxygen and paclitaxel loaded liposome mierobubbles plus ultrasound group （25 μL, 0.5 W/cm2, 30 s）. Cell viability was measured by MTF assay. The expression of HIF-1α at mRNA and protein levels was measured in the hypoxic macrophages by RT-PCR or Western blotting. ELISA was used to detect the levels of TNF-α and IL-6 secreted by the macrophages after treatments. Results Treatment of 100 μmol/L CoC12 for 12 h inhibited the cell viability in the RAW264.7 cells by less than 8% and successfully induced the cells into a hypoxic state. Oxygen and paclitaxel loaded liposome microbubbles mediated by ultrasound could significantly suppress the expression of HIF-1 α at mRNA and protein levels, and the secretions of TNF-α and IL-6 （P 〈 0. 05）. Conclusion Oxygen and paclitaxel loaded ]iposome microbubbles mediated by ultrasound effectively inhibits the expression of HIF-1 α in hypoxic macrophages, and attenuates the hypoxic state.
作者 崔健毓 朱深银 张烨 常淑芳 孙江川 邱峰 张成志 王志刚
机构地区 重庆医科大学附属第一医院药学部 重庆医科大学附属第二医院妇产科 重庆医科大学超声影像学研究所
出处 《第三军医大学学报》 CAS CSCD 北大核心 2016年第19期2128-2132,共5页 Journal of Third Military Medical University
基金 国家自然科学基金面上项目(81572558 81372799) 重庆市研究生科研创新项目(2015-139)~~
关键词 携氧载紫杉醇脂质微泡 巨噬细胞 缺氧诱导因子-1Α 类风湿关节炎 乏氧 oxygen and paclitaxel loaded liposome microbubbles macrophages hypoxia-induciblefactor-1α rheumatoid arthritis hypoxia
分类号 R392.12 [医药卫生—免疫学] R965.2 [医药卫生—药理学]
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参考文献15

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第三军医大学学报
2016年 第19期

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