Effect of RNA interference therapy on the mice eosinophils CCR3 gene and granule protein in the murine model of allergic rhinitis.
Effect of RNA interference therapy on the mice eosinophils CCR3 gene and granule protein in the murine model of allergic rhinitis.
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DOI：
10.1016/s1995-7645(14)60026-2
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发表时间：
2014-03
影响因子：
3.1
通讯作者：
Xinhua Zhu;B. Liao;Ke Liu;Yuehui Liu
中科院分区：
文献类型：
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作者：
Xinhua Zhu;B. Liao;Ke Liu;Yuehui Liu
目的观察变应性鼻炎小鼠的临床表现以及骨髓、外周血和鼻腔灌洗液中嗜酸性粒细胞CCR3和颗粒蛋白mRNA的表达变化。方法将24只BALB/c小鼠随机分为对照组、PBS治疗组、siRNA治疗组和CCR3 siRNA治疗组（n=6）。过敏性鼻炎模型采用ovalbunfin致敏刺激，CCR3 siRNA治疗组在刺激前经鼻给予CCR3。采用RT-PCR法检测骨髓、外周血和鼻腔灌洗液中嗜酸性粒细胞CCR3、MBP、ECP和EPO的水平。结果与对照组和CCR3 siRNA治疗组相比,PBS治疗组和siRNA治疗组鼻黏膜出现上皮细胞增生、杯状细胞增生、鳞状上皮化生、上皮坏死、固有层和粘膜下腺增生、血管舒张、组织水肿和特征性嗜酸性粒细胞浸润。 RT-PCR结果显示，CCR3 siRNA治疗组骨髓、外周血和鼻腔灌洗液中CCR3 mRNA、MBP、ECP、EPO表达量低于PBS治疗组和siRNA治疗组（P<0.05）。结论经鼻局部给药对CCR3的RNA干扰治疗可以抑制变应性鼻炎嗜酸性粒细胞的发展、迁移和侵袭过程，从而减轻嗜酸性粒细胞的作用。进而减轻过敏性鼻炎的炎症作用。它可能是治疗呼吸道过敏性炎症的新方法。
ObjectiveTo observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein mRNA in the bone marrow, peripheral blood and nasal lavage fluid.MethodsTwenty-four BALB/c mice were randomly divided into the control group, PBS therapy group, siRNA therapy group and the CCR3 siRNA therapy group (n=6). Allergic rhinitis model were sensitized and stimulated by ovalbunfin, and CCR3 siRNA therapy group were administered with CCR3 transnasally before stimulated. The levels of the eosinophils CCR3, MBP, ECP and EPO in bone marrow, peripheral blood and nasal lavage fluid were detected by RT-PCR.ResultsCompared to the control group and CCR3 siRNA therapy group, the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy, goblet cells hyperplasia, squamous epithelium metaplasia, epithelium necrosis, lamina propria and submucosa gland hyperplasia, vasodilatation, tissue edema, and the characterized eosinophil infiltration. RT-PCR indicated that the CCR3 mRNA, MBP, ECP and EPO expression in bone marrow, peripheral blood and nasal lavage fluid of the CCR3 siRNA therapy group was lower than the PBS therapy group and siRNA therapy group (P<0.05).ConclusionsThe RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development, migration and invasion of the allergic rhinitis eosinophil, thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis. It may be a new treatment for respiratory tract allergic inflammation.