IL-1β介导JNK信号转导通路对变应性鼻炎大鼠鼻黏膜组织重塑的影响及作用机制

Effect and mechanism of IL-1β/JNK transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats

目的:探讨IL-1β/JNK信号转导通路对变应性鼻炎(AR)大鼠鼻黏膜组织重塑的影响及作用机制。方法:将Wistar大鼠60只以随机数字表法分为AR组(A组)和对照组(B组)2组。A组以卵清蛋白(OVA)、氢氧化铝致敏和激发建立AR鼻黏膜重塑模型,根据致敏和激发时间不同,分为4、8、12周组(分别为A4、A8、A12组);同时设立相应B组(分别为B4、B8、B12组),以生理盐水代替OVA。ELISA法测定大鼠血清及鼻腔灌洗液中IL-1β浓度;免疫组织化学法检测鼻黏膜组织磷酸化JNK(P-JNK)及磷酸化c-Jun(P-c-Jun)蛋白平均吸光度值(mA值);Western Blot检测鼻腔组织匀浆P-JNK水平。对P-JNK mA值与血清及鼻腔灌洗液中IL-1β浓度进行直线相关分析。结果:A组4、8、12周大鼠血清及鼻腔灌洗液中IL-1β浓度均高于同时期B组(P<0.01),且A组鼻腔灌洗液中IL-1β浓度,12周时高于4周、8周(P<0.01);A组血清中IL-1β浓度在4、8、12周时差异无统计学意义(P>0.05)。A组各时期P-JNK及其P-c-Jun mA值均高于同期B组(P<0.01),且12周时二者均高于4、8周(P<0.01)。A组各时段P-JNK水平均高于同时期B组(P<0.01),且12周时均高于4、8周(P<0.01)。PJNK mA值与血清及鼻腔灌洗液中IL-1β浓度均呈显著正相关(r分别为0.835、0.902,P<0.01)。结论:JNK信号转导途径在AR大鼠鼻黏膜重塑中起到了重要作用;IL-1β可能通过介导JNK信号转导途径,参与AR鼻黏膜组织重塑的形成。

Objective：To study the role of JNK（c-Jun N-terminal kinase）signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats,to explore whether IL-1β participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway.Method：Totally 60 male Wistar rats（weighing about 200-250g）were randomly divided into A（AR group）and B group（control group）.The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al（OH）3.Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks（A4,A8,or A12group）,each had 10 rats.The rats in B group were sensitized by intraperitoneal injection saline.Saline was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks（B4,B8,or B12 group）,and each had 10 rats.The concentration of IL-1β in serum and nasal lavage fluid were tested by ELASA.The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique.Linear correlation analysis showed the correlation between levels of IL-1β in serum and P-JNK protein,levels of IL-1β in nasal lavage fluid and P-JNK protein.Result：The concentrations of IL-1β in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group（all P〈0.01）.Compared with A4 group and A8 group,concentrations of IL-1β in nasal lavage fluid of A12 group were significantly increased（all P〈0.01）.However the levels of IL-1β in serum were not significantly different among them（all P〉0.05）.Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group（all P〈0.01）,and compared with A4 group and A8 group,those of A12 group were significantly increased（all P〈0.01）.Strong positive correlation were found between P-JNK and concentration of IL-1β in serum or nasal lavage fluid（r=0.835 and r=0.902,all P〈0.01）.Conclusion：JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats.IL-1βparticipates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.