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RNA干扰疗法对变应性鼻炎小鼠模型中嗜酸性粒细胞CCR3基因及颗粒蛋白的影响

Effect of RNA interference therapy on the mice eosinophils CCR3 gene and granule protein in the murine model of allergic rhinitis.

作者信息

Zhu Xin-Hua, Liao Bing, Liu Ke, Liu Yue-Hui

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Department of Head and Neck Surgery, the Tumor Hospital of Jiangxi Province, Nanchang 330006, China.

出版信息

Asian Pac J Trop Med. 2014 Mar;7(3):226-30. doi: 10.1016/S1995-7645(14)60026-2.

DOI:10.1016/S1995-7645(14)60026-2
PMID:24507645
Abstract

OBJECTIVE

To 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.

METHODS

Twenty-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.

RESULTS

Compared 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).

CONCLUSIONS

The 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.

摘要

目的

观察变应性鼻炎小鼠的临床表现以及骨髓、外周血和鼻灌洗液中嗜酸性粒细胞趋化因子受体3(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)。采用卵清蛋白致敏和激发建立变应性鼻炎模型,CCR3 siRNA治疗组在激发前经鼻给予CCR3。采用逆转录聚合酶链反应(RT-PCR)检测骨髓、外周血和鼻灌洗液中嗜酸性粒细胞CCR3、髓过氧化物酶(MBP)、嗜酸性粒细胞阳离子蛋白(ECP)和嗜酸性粒细胞过氧化物酶(EPO)的水平。

结果

与对照组和CCR3 siRNA治疗组相比,PBS治疗组和siRNA治疗组小鼠鼻黏膜出现上皮脱落、杯状细胞增生、鳞状上皮化生、上皮坏死、固有层和黏膜下腺体增生、血管扩张、组织水肿,并伴有特征性的嗜酸性粒细胞浸润。RT-PCR结果显示,CCR3 siRNA治疗组骨髓、外周血和鼻灌洗液中CCR3 mRNA、MBP、ECP和EPO的表达低于PBS治疗组和siRNA治疗组(P < 0.05)。

结论

经鼻局部给予CCR3的RNA干扰疗法可抑制变应性鼻炎嗜酸性粒细胞的发育、迁移和浸润过程,从而降低嗜酸性粒细胞的作用,减轻变应性鼻炎的炎症反应。这可能是呼吸道变应性炎症的一种新的治疗方法。

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