从转染细胞活性Meta分析SPIO用于分子影像学研究的最佳浓度区间

Exploration of the optimal concentration range of SPIO through detecting transfection cell activity in the molecular imaging research:a Meta analysis

目的:通过检测转染细胞的活性,Meta分析超顺磁性氧化铁纳米(superparamagnetic iron oxide,SPIO)在分子影像学实验中用于转染细胞的最佳浓度区间。方法:系统检索国外(Pub Med、Embase、Cochrane Library)及国内主要数据库(万方、维普、中国知网及中国生物医学数据库)建库至2016年3月间关于SPIO转染细胞的最佳浓度区间的相关文献,结合Cochrane协作网的推荐,制定纳入研究文献的标准,对纳入文献进行质量评估并提取研究数据。采用STATA 12.0进行统计学分析:偏倚性检验(Begg’s检验)、异质性检验(I2、P值、Q值检验法),在异质性较大时行亚组分析,讨论各组异质性(I2、P值、Q值检验法),计算各组死细胞比率均差值在各浓度上的合并效应量及95%可信区间,并画出SPIO浓度对细胞活性影响的剂量反应曲线,获取最佳浓度区间。结果:共14篇国内外研究论著符合纳入标准,文献异质性检验I2=60.61%;P=2.675×10-9;Q=139.62,提示数据组间存在显著的异质性,故进一步行亚组分析,按SPIO修饰或标记材料不同分为4组[A组:SPIO-聚乙烯酰胺(PEI)组;B组:SPIO-多聚赖氨酸(PLL)组;C组:SPIO-葡聚糖组;D组:SPIO-探针组],各组数据无明显异质性;拟合各组各浓度节点死细胞比率均差值及95%可信区间,画出剂量反应曲线(三次样条插值拟合曲线),分别得到A至D组较适宜的浓度区间值:4~6、10~50、10~50、5~25μg/m L。Deeks漏斗图呈较对称漏斗形,P=0.23>0.1,表明数据无明显发表偏倚。结论:在分子影像学研究中,当SPIO由聚乙烯酰胺(PEI)、葡聚糖、葡聚糖-多聚赖氨酸(PLL)包裹或制备为探针时,以SPIO对细胞的毒性影响为主要衡量指标,标记细胞的适宜浓度区间分别为:4~6、10~50、10~50、5~25μg/m L。

Objective：To explore the optimal concentration range of super-paramagnetic iron oxide （SPIO） of transfecting cell in the molecular imaging experiments by detecting transfection cell activity. Methods：Search in PubMed, Embase, Cochrane Library, CNKI, VIP, CBM and Wan Fang was performed to identify relevant English and Chinese language articles, respectively. Criteria for inclusion, quality evaluation and extract the data were established based on validity criteria published by the Cochrane Methods Group. STATA 12.0 was used for statistical analysis. Bias test （Begg＇s inspection） ,heterogeneity inspection （12,P,Q test） was.used to discuss the heterogeneity of groups,calculate the fitting values and lower and upper bounds,draw the dose-response curve,and obtain the optimal concentration range. Results：Fourteen articles were included. Funnel plot was symmetrical indicating no significant publication bias. The heterogeneity inspection （ F=60.61% ; P=2.675 × 10^-9; Q = 139.62） showed a significant heterogeneity. Subgroup analysis was conducted and all Subjects were divided into four groups（A to D groups） according to the different materiasl;subgroup analysis showed no obvious heterogeneity among groups. The fitting values and lower and upper bounds were calculated, the dose-response curve wasdrew,and the optimal concentration range of each groups was obtained. Conclusion：In the molecular imaging experiments, when SPIO fitting by PEI, dextran, dextran-PLL or prepared for the probe,the optimal concentration ranges are：4 to 6 μg/mL, 10 to 50 μg/mL, 10 to 50 μg/mL,5 to 25 μg/mL.