Zang Hong-rui, Wang Tong, Fan Er-zhong, Li Ying, Zhou Bing
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Otorhinolaryngology, Beijing 100730, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009 Jun;44(6):499-503.
To evaluate the effect of intranasal liposome-mediated IL-12 gene therapy on the eosinophils and IL-5 in the murine model of allergic rhinitis.
Thirty-six BALB/C mice were randomly divided into allergic rhinitis (AR) group, gene therapy group and control group. Allergic rhinitis group were sensitized and stimulated by ovalbumin (OVA), and gene therapy group were administered with liposome-mediated pGEG. mIL-12 transnasally before stimulated. The eosinophils in bone marrow were counted by Wright's staining, and the eosinophils in nasal mucosa were counted by HE staining. The eosinophils of peripheral blood were detected by flow cytometry. The expression of IL-5 in bone marrow and nasal mucosa was examined by immunohistochemistry. The IL-5 in serum was detected by ELISA.
Among the three groups, the difference of all data was statistically significant (P<0.01). Multiple Comparison showed that the ratio of eosinophils to white cells and the mount of IL-5 positive cells in nasal mucosa and bone marrow of gene therapy group was significantly lower than that of AR group (P<0.05). The ratio of eosinophils to granulocyte (0.124 +/- 0.031) and the expression level of IL-5 [(29.51 +/- 6.68) pg/ml] in peripheral blood [ 0.184 +/- 0.079 and (56.58 +/- 16.80) pg/ml] were significantly lower in gene therapy group than in AR group (P<0.05).
Transnasal administration of liposome- mediated pGEG. mIL-12 could depress the expression of IL-5 in bone marrow, peripheral blood, and nasal mucosa, to influence the proliferation and differentiation of eosinophils and decrease the delivery and transference of eosinophils to peripheral blood and nasal mucosa. It may be a new treatment for respiratory tract allergic inflammation.
评估鼻内脂质体介导的白细胞介素-12（IL-12）基因治疗对变应性鼻炎小鼠模型中嗜酸性粒细胞及IL-5的影响。
将36只BALB/C小鼠随机分为变应性鼻炎（AR）组、基因治疗组和对照组。AR组用卵清蛋白（OVA）致敏和激发，基因治疗组在激发前经鼻给予脂质体介导的pGEG.mIL-12。采用瑞氏染色法计数骨髓中的嗜酸性粒细胞，苏木精-伊红（HE）染色法计数鼻黏膜中的嗜酸性粒细胞。采用流式细胞术检测外周血嗜酸性粒细胞。采用免疫组织化学法检测骨髓和鼻黏膜中IL-5的表达。采用酶联免疫吸附测定（ELISA）法检测血清中IL-5。
三组间所有数据差异均有统计学意义（P<0.01）。多重比较显示，基因治疗组鼻黏膜和骨髓中嗜酸性粒细胞与白细胞的比例及IL-5阳性细胞数量均显著低于AR组（P<0.05）。基因治疗组外周血中嗜酸性粒细胞与粒细胞的比例（0.124±0.031）及IL-5表达水平[（29.51±6.68）pg/ml]显著低于AR组[0.184±0.079及（56.58±16.80）pg/ml]（P<0.05）。
经鼻给予脂质体介导的pGEG.mIL-12可抑制骨髓、外周血和鼻黏膜中IL-5的表达，影响嗜酸性粒细胞的增殖和分化，减少嗜酸性粒细胞向外周血和鼻黏膜的输送与转移。这可能是呼吸道变应性炎症的一种新治疗方法。
