类过敏反应体外评价模型的建立及其指标的筛选

发布时间：2018-02-25 04:13

  本文关键词： 类过敏反应 RBL-H细胞 Pl细胞 Ku细胞 体外　出处：《中国新药杂志》2017年14期 　论文类型：期刊论文

【摘要】：目的:以C48/80为阳性药物,比较3种细胞系(RBL-2H3,P8l5和Ku812细胞)及其指标在评价药物类过敏中的敏感性;并采用聚山梨酯80对3种细胞模型评价类过敏反应的适用性进行考察。方法:以不同浓度的C48/80分别作用于3种细胞系30和60 min,测定β-氨基糖苷酶释放率、Annexin V阳性细胞率以及IL-4和TNF-α释放量。然后,用聚山梨酯80进行模型的适用性考察,同时对不同浓度的聚山梨酯80引起的类过敏反应进行评价。结果:C48/80可引起3种细胞系的β-氨基糖苷酶释放率、Annexin V阳性细胞率、IL-4释放量和TNF-α释放量呈剂量依赖性增加;除了RBL-2H3细胞,其他2个细胞系检测到的IL-4释放量非常少,且3种细胞系检测到的TNF-a量亦非常少;Annexin V阳性细胞率的增加程度较其他3项指标明显;在相同刺激条件下,P815和Ku812细胞的β-氨基糖苷酶释放率和Annexin V阳性细胞率的突增较RBL-2H3细胞发生时间早,突增效果更明显。聚山梨酯80的结果与C48/80给药时基本吻合。此外,还发现聚山梨酯80≥0.05 mg·m L~(-1)时,即存在引起类过敏反应的风险。结论:β-氨基己糖苷酶释放率和Annexin V阳性细胞率是评价类过敏反应的2种稳定、可靠、重复性好的检测指标;IL-4释放量和TNF-α释放量较适合作为辅助检测指标;Annexin V阳性率可较敏感地、较早地提示类过敏反应的发生。P815和Ku812细胞较RBL-2H3细胞更适合作为一种早期、稳定、敏感的肥大细胞脱颗粒体外检测模型,用于致类过敏反应药物的早期筛选。
[Abstract]:Objective: to compare the sensitivity of three cell lines (RBL-2H3P8l5 and Ku812) with C48 / 80 in evaluating drug allergy. The applicability of polysorbate 80 to three cell models to evaluate the anaphylaxis reaction was investigated. Methods: three cell lines were treated with different concentrations of C48 / 80 for 30 min and 60 min, respectively. The release rate of 尾-aminoglycosidase and Annexin V positive rate were measured. Cell rate and release of IL-4 and TNF- 伪. Then, The applicability of the model was investigated with polysorbate 80. At the same time, the anaphylaxis reaction induced by different concentrations of polysorbate 80 was evaluated. Results the release rate of 尾 -aminoglycosidase and the release rate of Annexin V positive cells were increased in a dose-dependent manner. In addition to RBL-2H3 cells, the IL-4 emission from the other two cell lines was very low, and the TNF-a quantity detected by the three cell lines was also very small. The increase of the TNF-a positive rate of the three cell lines was significantly higher than that of the other three indexes. The 尾 -glucosaminidase release rate and Annexin V positive cell rate of P815 and Ku812 cells were increased earlier than that of RBL-2H3 cells under the same stimulation conditions. The results of polysorbate 80 were consistent with those of C48 / 80. It was also found that when polysorbate 80 鈮，

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