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目的研究卡介菌多糖-核酸(BCG-PSN)的抗I型过敏反应作用,并探讨其可能的作用机制。方法建立卵白蛋白致敏大鼠血清引起的大鼠同种被动皮肤过敏反应(PCA)模型、磷酸组胺诱导的大鼠皮肤血管通透性升高模型、低分子右旋糖酐诱导的小鼠全身皮肤瘙痒模型,探讨BCG-PSN在体抗I型过敏反应作用;卵白蛋白致敏大鼠腹腔肥大细胞主动脱颗粒试验法探讨BCG-PSN离体抗I型过敏反应作用;ELISA法检测外周血中IL-4、IFN-γ水平和IgE抗体滴度,探讨BCG-PSN抗I型过敏反应可能的作用机制。结果大鼠隔日肌内注射BCG-PSN(0.026,0.077,0.232mg·kg-1)3wk、小鼠隔日肌内注射BCG-PSN(0.025,0.075,0.225mg·kg-1)3wk,均可剂量依赖性抑制卵白蛋白诱导的大鼠PCA,缓解低分子右旋糖酐诱导的小鼠全身皮肤瘙痒,对磷酸组胺诱导的大鼠皮肤血管通透性增高无影响;BCG-PSN(10-6mg·mL-1～10-3mg·mL-1)可浓度依赖性抑制卵白蛋白诱导的肥大细胞脱颗粒反应,最大抑制率为69.12%,抑制肥大细胞脱颗粒反应的半数抑制浓度(IC50)为7×10-5mg·mL-1;与生理盐水对照组比较,BCG-PSN三个剂量组1∶2、1∶8、1∶32三个血清稀释度蓝斑平均OD值均明显降低(P<0.05),外周血中IL-4水平明显降低(P<0.05),IFN-γ水平明显升高(P<0.05)。结论BCG-PSN可剂量依赖性抑制I型过敏反应作用,其抗I型过敏反应的可能机制与抑制血清IgE的生成,减少外周血中IL-4水平,增加外周血中IFN-γ水平有关。
Objective To study the anti-type I anaphylactic reaction induced by BCG polysaccharide-nucleic acid (BCG-PSN) and to explore its possible mechanism. Methods A rat model of allogeneic passive cutaneous anaphylaxis (PCA) caused by ovalbumin-sensitized rat serum was established. The histamine-induced phosphate-induced hyperosmolarity in rat skin was induced by low molecular weight dextran PSN in vitro. The anti-allergic reaction of BCG-PSN was observed in vitro. The anti-allergic reaction of BCG-PSN in vitro was detected by active degranulation of ovalbumin-sensitized rat peritoneal mast cells. The level of IL- 4, IFN-γ levels and IgE antibody titers to explore the possible mechanism of BCG-PSN anti-type I anaphylaxis. Results The rats were intramuscularly injected with BCG-PSN (0.026,0.077,0.232mg · kg-1) for 3 weeks every other day. The mice were intramuscularly injected with BCG-PSN (0.025,0.075,0.225mg · kg-1) for 3 weeks, Dependent inhibition of ovalbumin-induced rat PCA, alleviating low-molecular dextran-induced systemic skin pruritus in mice and no effect on histamine-induced increase of rat skin vascular permeability. BCG-PSN (10-6 mg · mL- 1 ~ 10-3mg · mL-1) inhibited the ovalbumin-induced mast cell degranulation in a concentration-dependent manner with the maximum inhibitory rate of 69.12% and the IC50 of inhibit mast cell degranulation of 7 × 10- 5mg · mL-1. Compared with the saline control group, the average OD values of the three serum dilutions at 1: 2,1: 8,1: 32 BCG-PSN were significantly decreased (P <0.05) The level of IL-4 in peripheral blood was significantly lower (P <0.05) and the level of IFN-γ was significantly higher (P <0.05). Conclusion BCG-PSN can inhibit the type I anaphylactic reaction in a dose-dependent manner. The possible mechanism of anti-type I allergic reaction is to inhibit the production of IgE, reduce the level of IL-4 in peripheral blood and increase the level of IFN-γ in peripheral blood.