Toll样受体9配体CpG-ODN鼻内应用对变应性联合气道疾病炎性反应的影响
本文选题:支气管哮喘 切入点:变应性鼻炎 出处:《中国病理生理杂志》2016年10期
【摘要】:目的:探讨免疫刺激序列Cp G寡聚脱氧核苷酸(Cp G-ODN)鼻内应用与皮下注射对变应性联合气道疾病(ACAD)模型小鼠下气道炎性反应的影响。方法:30只清洁级雌性BALB/c鼠随机分为正常对照组(control组)、变应性鼻炎组(AR组)、变应性联合气道疾病组(ACAD组)、变应性联合气道疾病Cp G-ODN鼻内滴入组(Cp G i.n.组)和变应性联合气道疾病Cp G-ODN皮下注射组(Cp G i.d.组)。实验组动物依次进行腹腔卵白蛋白(OVA)和氢氧化铝凝胶基础致敏和3次鼻腔激发,此后OVA或生理盐水(NS)雾化气道激发,正常对照组则给予NS。Cp G i.n.组和Cp G i.d.组分别给予10.0μg Cp G-ODN滴鼻和皮下注射,其它组给予NS滴鼻或皮下注射。观察Cp GODN干预后对鼻腔及下气道病理变化及评分,并对支气管肺泡灌洗液(BALF)行白细胞分类及嗜酸性粒细胞计数,ELISA法测定BALF和脾脏中细胞因子IL-4、IL-5、IL-13和IFN-γ,以及血清OVA特异性Ig E。结果:炎症细胞浸润评分示ACAD组小鼠肺部的病理改变程度高于control组和AR组(P0.01);Cp G i.n.组炎症评分较ACAD组下降,差异有统计学显著性(P0.05),而Cp G i.d.组炎症评分较ACAD组略有下降,但差异无统计学意义。Cp G i.n.组BALF中的白细胞总数、EOS绝对值计数、EOS百分比、BALF和脾脏淋巴细胞上清液中Th2细胞因子较ACAD组降低,差异具有统计学显著性(P0.01)。Cp G i.d.组上述指标略低于ACAD组,但差异无统计学显著性。Cp G i.n.组血清的OVA特异性Ig E较ACAD组下降,差异有统计学显著性(P0.05),而Cp G i.d.组与ACAD组比较有所下降,但差异无统计学显著性。结论:Cp G-ODN可通过抑制变应性鼻炎而抑制变应性联合气道疾病小鼠的下气道炎性反应,鼻内应用可能较皮下注射更有效。
[Abstract]:Objective: to investigate the effect of intranasal application and subcutaneous injection of CpG oligodeoxynucleotide oligodeoxynucleotides (CpG-ODN) on the inflammatory response of inferior airway in mice with allergic combined airway disease and ACAD.Methods: 30 clean female BALB/c mice were randomly assigned. The patients were divided into normal control group, allergic rhinitis group and AR group, allergic combined airway disease group with ACAD group, allergic combined airway disease CP G-ODN intranasal drip group with CpG i.n.) and allergic combined airway disease subcutaneous injection group with CP G-ODN. The experimental group was sensitized by ovalbumin (OVA), aluminum hydroxide gel and nasal cavity three times. After that, OVA or normal saline (NS) atomized airway was stimulated, while the normal control group was given 10.0 渭 g CP G-ODN intranasal drip and subcutaneous injection, while the normal control group was given NS.Cp G i.n. and CP G i.d. group, respectively. Other groups were given NS nasal drip or subcutaneous injection. The pathological changes and scores of nasal cavity and lower airway were observed after CP GODN intervention. Leukocyte classification and eosinophilic granulocyte count Elisa were performed on bronchoalveolar lavage fluid (BALF) to detect BALF, IL-4, IL-5, IL-13 and IFN- 纬, as well as serum OVA specific Ig E.Results: inflammatory cell infiltration score showed lung of ACAD group mice. The degree of pathological changes in control group and AR group was higher than that in ACAD group, and the inflammatory score in CP G i.n. group was lower than that in ACAD group. The inflammatory score of CP G i.d. group was slightly lower than that of ACAD group. However, there was no significant difference in the absolute value of total white blood cell count in BALF and the percentage of Th2 cytokines in the supernatant of spleen lymphocytes and the percentage of Th2 in the supernatant of spleen lymphocytes in group C. CpG i.n. was lower than that in group ACAD. The difference was statistically significant (P 0.01) .CpG i.d. the above indexes were slightly lower than those in ACAD group, but there was no significant difference in OVA specific IgE between ACAD group and CpG i.d. group. The difference was statistically significant (P 0.05), while that of CP G i.d. group was lower than that of ACAD group, but the difference was not statistically significant. Conclusion the lower airway inflammatory response of mice with allergic rhinitis can be inhibited by inhibiting allergic rhinitis. Intranasal administration may be more effective than subcutaneous injection.
【作者单位】: 中山大学附属第三医院呼吸内科中山大学呼吸疾病研究所;中山大学附属第三医院儿科;中山大学附属第三医院耳鼻咽喉头颈外科;
【基金】:国家自然科学基金资助项目(No.81470220) 广东省自然科学基金资助项目(No.S2013010015990)
【分类号】:R56;R765.21
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