摘要
目的长期慢性炎症导致鼻黏膜重塑特征表现为基膜内胶原沉积。文中探讨与胶原沉积相关的基质金属蛋白酶(matrix metalloproteinase,MMP)-9/组织金属蛋白酶抑制剂(tissue inhibitors of metalloproteinase,TIMP)-1在鼻致敏豚鼠模型鼻黏膜重塑中的作用。方法 Hartley系豚鼠32只,随机分为4组,即实验2w组、6w组、12w组和对照组。卵清蛋白(ovalbumin,OVA)制备变应性鼻炎动物模型,抗原刺激分别持续2w、6w和12w。鼻黏膜组织切片,采用HE染色,计数鼻黏膜嗜酸性粒细胞数量。免疫组化法检测鼻黏膜Ⅰ型胶原、MMP-9和TIMP-1含量。结果①实验2w组、实验6w组、实验12w组和对照组下鼻甲嗜酸粒细胞计数分别为:50.75±11.75、56.63±7.46、66.13±8.72和8.00±3.91(个/高倍视野),与对照组比较,其他各组差异有统计学意义(P<0.01)。②与对照组比较,实验2w组、6w组、12w组鼻黏膜的Ⅰ型胶原、MMP-9和TIMP-1的吸光度随抗原刺激时间延长均有升高趋势;实验各组的MMP-9/TIMP-1吸光度比值与对照组比较有下降趋势,尤其在实验12w组,其差别有统计学意义(P<0.01)。结论随着抗原刺激延长,鼻黏膜慢性炎症导致与重塑有关的MMP-9和TIMP-1免疫活性增强,MMP-9/TIMP-1的失衡,从而使得细胞外基质(extracellular matrix,ECM)中胶原蛋白沉积。
Objective Nasal mucosa remodeling was identified with collagen deposition in basal membrane resulting from long-term chronic inflammation. The aim of this study was to explore the role of matrix metalloproteinase-9 （MMP-9） / tissue inhibitors of metalloproteinase-1 （TIMP-1） in nasal mucosa remodeling in a guinea pig model of prolonged allergic-induced rhinitis. Methods Thirty-two male Hartley guinea pigs were randomly divided into four groups. Allergen challenged groups （ Group2w, Group6w and Group12w ） and a control group. To develop a guinea pig model of nasal mucosa remodeling, ovalbumin-sensitized guinea pigs were re- peatedly challenged with allergen twice a week from two weeks to 12 weeks. Matched control groups were challenged with physiological saline. Nasal mucosa were obtained by killed the animals. Hematoxylin-Eosin （ HE）, and immunohistochemical staining against colla gen I ,MMP-9 and TIMP-1 were performed with nasal mucosa. Results （1）Pathological examination showed obvious infiltration of e osinophils in the experiment groups. （2） The values of absorbance of Collagen I in the experiment groups （ Group 2w, 6w and 12w） were O. 304 ±0. 113, 0. 333± 0. 091 and O. 358 ±0. 099 （ compared with control group, the values of P were respectively O. 212, 0. 903 and 0. 048）. The values of absorbance of MMP-9 in the experiment groups were 0. 247 ± 0.068, 0. 328 ± 0.054 and 0.258 ± 0. 068 （ compared with control group, the values of P were respectively 0. 219±0. 001, and 0. 123 ）. The values of absorbanee of TIMP-9 in the experiment groups were 0.261 ± 0. 057, 0. 372 ± 0. 031 and 0. 333 ± 0. 053 （ compared with control group, the values of P were respectively 0. 032, 0. 095 and 0. 005 ）. The ratio of absorbanee of MMP-9/TIMP-1 showed a decreasing trend along pro longed allergen challenged in the experiment groups. Conclusion Along challenge of allergen prolonged and inflammation of nasal mucosa being worse, the immunoactivitv of MMP-9 and TIMP-1 may be strenathened, the ratio of absorbance of MMP-9/TIMP-1 mavbedisbalanced, and result in collagen deposited within the extracellular matrix in nasal mucosa.
出处
《医学研究生学报》
CAS
北大核心
2014年第1期23-26,共4页
Journal of Medical Postgraduates
基金
江苏省基础研究计划面上项目(BK2006134)
关键词
变应性鼻炎
细胞外基质
胶原
基质金属蛋白酶9
组织金属蛋白酶抑制剂1
Allergic rhinitis
Extracellular matrix
Colla-gen
Matrix metalloproteinase-9
Tissue in-hibitors of metalloproteinase-1
