摘要
目的 探索T细胞免疫球蛋白黏蛋白分子4 (T cell immunoglobulin and mucin domain molecule4,TIM4)在变应性鼻炎(allergic rhinitis,AR)发病中的作用机制,为AR的治疗提供新思路和新靶点.方法 BALB/C雄性实验小鼠21只完全随机平均分为3组,分别为对照组、AR组及TIM4抗体干预组.AR模型采用卵清蛋白(ovalbumin,OVA)进行基础致敏和鼻腔局部滴鼻激发;采用行为学观察结合免疫学及鼻黏膜HE染色进行AR评估和监测.通过免疫荧光和反转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)方法,研究TIM4在不同组别小鼠鼻黏膜局部的表达.以SPSS 18.0软件进行统计结果的数据分析.结果 小鼠AR模型制作成功.AR组、对照组、TIM4抗体干预组小鼠鼻黏膜TIM4 mRNA的相对表达量分别为16.29±3.80、0.51 ±0.60、1.64±0.98,3组差异有统计学意义(F=46.56,P<0.05);AR组显著高于对照组和TIM4抗体干预组,差异有统计学意义(t值分别为8.650、8.027,P值均<0.05);而对照组与TIM4抗体干预组之间TIM4mRNA表达差异无统计学意义(t=-0.623,P>0.05).AR小鼠鼻黏膜局部高表达TIM4,其表达部位主要集中在假复层纤毛柱状上皮下层.结论 TIM4在AR发病过程中可能发挥了重要的作用,有效抑制TIM4的表达,可能可以延缓或部分逆转AR的病理过程.
Objective To investigate the role of TIM4 (T cell immunoglobulin and mucin domainmolecule 4) in the pathogenesis of allergic rhinitis (AR) in mice,and to identify a novel therapeutic target for the treatment of AR.Methods Twenty-one male BALB/C mice of clean grade were divided into three groups randomly (n =7 per group) including control,AR and anti-TIM4 antibody treatment groups.In order to induce upper airway allergic inflammation,the mice from AR and anti-TIM4 antibody treatment groups were sensitized by intraperitoneal injection followed by intranasal challenge with ovalbumin.Before the ovalbumin challenge,a group of mice was treated with anti-TIM4 antibody.To assess the AR model,behavioral observation with immunological assessments and HE staining of nasal tissues were performed.The TIM4 expression in nasal tissues in different groups of mice were assessed by immunofluorescence and RTPCR.SPSS18.0 software was used to analyze the data.Results The AR model in mice was successfully established as shown by behavioral observation and immunological evaluation.RT-PCR assays showed the relative expression of TIM4 mRNA in nasal mucosa of AR,control and anti-TIM4 antibody treatment mice was 16.29 ±3.80,0.51 ±0.60,1.64 ±0.98,respectively.There was statistically significant differencea mong three group (F =46.56,P < 0.05).The expression of TIM4 in AR group was significantly higher than those in control group (t =8.650,P < 0.05) and anti-TIM4 group (t =8.027,P < 0.05).The expression of TIM4 was significantly reduced in the anti-TIM4 antibody group,as well as control group (t =-0.623,P > 0.05).More expression of TIM4 was detected in local nasal tissues of AR mice,mainly located below the pseudostratified ciliated columnar epithelium.Conclusions TIM4 plays a crucial role in the pathogenesis of AR.Effective inhibition of TIM4 expression can partially reverse the pathological changes of AR.
出处
《中华耳鼻咽喉头颈外科杂志》
CAS
CSCD
北大核心
2014年第4期283-287,共5页
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
基金
国家自然科学基金(81070767、81271059)
山西省回国留学人员科研资助项目(2010-56)
山西省高校科技研究开发项目(20101145)
山西医科大学第二医院青年基金(20130103)