核因子κＢ在分泌性中耳炎动物模型鼓室黏膜中的表达及PDTC对其表达的影响
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摘要
目的检测核因子-κB(nuclear factorκB,NF-κB)在分泌性中耳炎(secretory otitis media,SOM)动物模型鼓室黏膜中的表达,探讨NF-κB活化在SOM发病机制中的作用。方法应用灭活肺炎链球菌,注入豚鼠中耳腔,制作SOM动物模型,采用免疫组化的方法检测:致病鼠鼓室黏膜上皮在注入细菌6h、1d、3d、7d及14d中NF-κBp65,TNF-α和IL-1β的表达及关系。结果SOM动物模型的鼓室黏膜上皮中NF-κBp65在术后六小时就有表达,24小时表达最强,随后表达明显下降,TNF-α和IL-1β的表达也出现相应波动。结论灭活肺炎链球菌致SOM的早期,NF-κB即被激活,在鼓室黏膜中出现过度表达,并与SOM发病中的重要致炎因子TNF-α和IL-1β的产生相关,提示NF-κB与SOM发病机制密切相关。
目的探讨NF-κB在分泌性中耳炎(secretory otitis media, SOM)发病机制中的作用,为临床探寻以NF-κB为靶点的治疗SOM提供实验依据。方法将76只豚鼠随机分三组:对照组(10只),SOM组(22只)和吡咯醛二硫氨基甲酸(pyrrolidine dithiocarbamat,PDTC)组(44只)。对照组:右耳注入0.9%生理盐水0.1ml,分别于0h,6h,1d,3d,5d各处死2只。SOM组:动物模型经右鼓室内注入灭活肺炎链球菌完成造模。PDTC组:右鼓室注入细菌后6h分别给予PDTC50mg/kg (PDTC1组)和200mg/kg(PDTC2组)腹腔注射。SOM组、PDTC组按注入细菌后不同时点0h, 6h,1d,3d,5d分别处死五只。通过免疫组化的方法检测鼓室黏膜NF-κB,TNF-α和IL-1β的表达,并行组织学观察。结果SOM组:NF-κBP65,TNF-α,IL-1β在6h就有表达,三者均于24h表达最强。3-5d鼓室粘膜明显增厚,大量炎性细胞浸润。PDTC1组:各时间段与SOM组表达相似,仅于1dNF-κBP65表达较低,两者差异(P<0.05)有显著性。PDTC2组NF-κBP65,TNF-α,IL-1β在6h表达与SOM组表达相似,1d,3d,5d有表达,但均低于SOM组(P<0.01)。3d-5d鼓室粘膜厚度明显低于SOM组(P<0.01),两组之间的差异具有非常显著性的意义。结论(1) NF-κB信号通路激活可能为SOM发病机制之一。SOM早期NF-κB活化可能与TNF-α和IL-1β上调密切相关。(2)抗氧化剂PDTC可抑制豚鼠SOM动物模型鼓室黏膜上皮NF-κB的活化,两者存在量,效依赖关系,早期足量PDTC干预可明显抑制NF-κB的活化。(3)抑制NF-κB的活化可下调SOM重要致炎因子TNF-α和IL-1β的表达,从而减轻SOM的病理改变。
Objective To explore the expression of nuclear factorκB (NF-κB) in the middle ear mucosa of guinea pigs with secretory otitis media (SOM) and the role of NF-κB in the development of SOM。Method SOM were produced by injecting deactivated streptococcus pneumonia(SP) into the typmpanic cavity of guinea pigs。The expression of NF-κBp65,TNF-α,and IL-1βwas examined by means of immunohistochemistry 6h,1D,3D,7D,and 14D after injection。Result NF-κBp65 expression could be detected in the middle ear mucosa as early as 6h after injection,and reached maximum at 24h after injection。The expression pattern of TNFαandIL-1βwas similar to that of NF-κB。Conclusion NF-κB was activated in the early stage of SOM induced by deactivated SP。Moreover, NF-κB could induceTNF-αandIL-1βexpression。It indicates that NF-κB may have an important role in the pathogenesis of SOM。
Objective To study the role of nuclear factor–κB(NF-κB) in the pathogenesis of secretory otitis media (SOM), and provided reliable experiment foundation for clinical treatment。Methods 76 guinea pigs were randomly divided into 3 groups: control group(10), SOM group(22) and pyrrolidine dithiocarbamat(PDTC) group(44)。The control guinea pigs were executed after right ear was injected with 0.9% sodium chloride。SOM models were produced by injecting deactivated streptococcus pneumonia into the right tympanic cavity of guinea pigs。In PDTC treated group, guinea pigs were injected intraperitoneally with PDTC at the dosages of 50 mg/kg (PDTC1 group) or 200mg。kg-1(PDTC2 group) respectively 6 hour after deactivated streptococcus pneumonia injection。。In SOM and PDTC treated group, guinea pigs were executed at 0h ,6 h, 1d, 3d , and 5d after bacteria injection。the expressions oTNF-κB, TNF-α, and IL-1βin the tympanic membrane were examined by means of immunohistochemistry。Result In SOM group, NF-κBP65,TNF-α,IL-1βcould be detected in the middle ear mucosa as early as 6h after bacteria injection , and reached maximum at 24h。Mucosa was obviously thickened in 3d to 5d。In PDTC1 group, the expression oTNF-κBP65,TNF-α,IL-1βwere similar with that in SOM group at different time points except 24h after bacteria injection。At 24 hour after injection , the level oTNF-κBP65 was lower than that in SOM group(P<0.01)。In PDTC2 group, NF-κBP65,TNF-α,IL-1βwere similar with that in SOM group at 6h。while as the expression was lower than that in SOM group at other time points。(P<0.01)。Moreover, the level of the thickness of mucosa of middle ear was lower than that in SOM group。Conclusion the results indicates that NF-κB may play an important role in the pathogenesis of SOM。NF-κB is activated in the early stage of SOM and can promote the expression of TNF-αand IL-1β。PDTC ,a NF-κB inhibitor can inhibit the expression of inflammatory mediators and the development of SOM。NF-κB inhibitors may have a potential benefit in the treatment of SOM
目的探讨NF-κB在分泌性中耳炎(secretory otitis media, SOM)发病机制中的作用,为临床探寻以NF-κB为靶点的治疗SOM提供实验依据。方法将76只豚鼠随机分三组:对照组(10只),SOM组(22只)和吡咯醛二硫氨基甲酸(pyrrolidine dithiocarbamat,PDTC)组(44只)。对照组:右耳注入0.9%生理盐水0.1ml,分别于0h,6h,1d,3d,5d各处死2只。SOM组:动物模型经右鼓室内注入灭活肺炎链球菌完成造模。PDTC组:右鼓室注入细菌后6h分别给予PDTC50mg/kg (PDTC1组)和200mg/kg(PDTC2组)腹腔注射。SOM组、PDTC组按注入细菌后不同时点0h, 6h,1d,3d,5d分别处死五只。通过免疫组化的方法检测鼓室黏膜NF-κB,TNF-α和IL-1β的表达,并行组织学观察。结果SOM组:NF-κBP65,TNF-α,IL-1β在6h就有表达,三者均于24h表达最强。3-5d鼓室粘膜明显增厚,大量炎性细胞浸润。PDTC1组:各时间段与SOM组表达相似,仅于1dNF-κBP65表达较低,两者差异(P<0.05)有显著性。PDTC2组NF-κBP65,TNF-α,IL-1β在6h表达与SOM组表达相似,1d,3d,5d有表达,但均低于SOM组(P<0.01)。3d-5d鼓室粘膜厚度明显低于SOM组(P<0.01),两组之间的差异具有非常显著性的意义。结论(1) NF-κB信号通路激活可能为SOM发病机制之一。SOM早期NF-κB活化可能与TNF-α和IL-1β上调密切相关。(2)抗氧化剂PDTC可抑制豚鼠SOM动物模型鼓室黏膜上皮NF-κB的活化,两者存在量,效依赖关系,早期足量PDTC干预可明显抑制NF-κB的活化。(3)抑制NF-κB的活化可下调SOM重要致炎因子TNF-α和IL-1β的表达,从而减轻SOM的病理改变。
Objective To explore the expression of nuclear factorκB (NF-κB) in the middle ear mucosa of guinea pigs with secretory otitis media (SOM) and the role of NF-κB in the development of SOM。Method SOM were produced by injecting deactivated streptococcus pneumonia(SP) into the typmpanic cavity of guinea pigs。The expression of NF-κBp65,TNF-α,and IL-1βwas examined by means of immunohistochemistry 6h,1D,3D,7D,and 14D after injection。Result NF-κBp65 expression could be detected in the middle ear mucosa as early as 6h after injection,and reached maximum at 24h after injection。The expression pattern of TNFαandIL-1βwas similar to that of NF-κB。Conclusion NF-κB was activated in the early stage of SOM induced by deactivated SP。Moreover, NF-κB could induceTNF-αandIL-1βexpression。It indicates that NF-κB may have an important role in the pathogenesis of SOM。
Objective To study the role of nuclear factor–κB(NF-κB) in the pathogenesis of secretory otitis media (SOM), and provided reliable experiment foundation for clinical treatment。Methods 76 guinea pigs were randomly divided into 3 groups: control group(10), SOM group(22) and pyrrolidine dithiocarbamat(PDTC) group(44)。The control guinea pigs were executed after right ear was injected with 0.9% sodium chloride。SOM models were produced by injecting deactivated streptococcus pneumonia into the right tympanic cavity of guinea pigs。In PDTC treated group, guinea pigs were injected intraperitoneally with PDTC at the dosages of 50 mg/kg (PDTC1 group) or 200mg。kg-1(PDTC2 group) respectively 6 hour after deactivated streptococcus pneumonia injection。。In SOM and PDTC treated group, guinea pigs were executed at 0h ,6 h, 1d, 3d , and 5d after bacteria injection。the expressions oTNF-κB, TNF-α, and IL-1βin the tympanic membrane were examined by means of immunohistochemistry。Result In SOM group, NF-κBP65,TNF-α,IL-1βcould be detected in the middle ear mucosa as early as 6h after bacteria injection , and reached maximum at 24h。Mucosa was obviously thickened in 3d to 5d。In PDTC1 group, the expression oTNF-κBP65,TNF-α,IL-1βwere similar with that in SOM group at different time points except 24h after bacteria injection。At 24 hour after injection , the level oTNF-κBP65 was lower than that in SOM group(P<0.01)。In PDTC2 group, NF-κBP65,TNF-α,IL-1βwere similar with that in SOM group at 6h。while as the expression was lower than that in SOM group at other time points。(P<0.01)。Moreover, the level of the thickness of mucosa of middle ear was lower than that in SOM group。Conclusion the results indicates that NF-κB may play an important role in the pathogenesis of SOM。NF-κB is activated in the early stage of SOM and can promote the expression of TNF-αand IL-1β。PDTC ,a NF-κB inhibitor can inhibit the expression of inflammatory mediators and the development of SOM。NF-κB inhibitors may have a potential benefit in the treatment of SOM
引文
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