【摘要】 目的探讨慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)患者中鼻甲黏膜环氧合酶2(cyclooxygenase 2,COX-2)与丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)及核因子κB(nuclear factor kappa B,NF-κB)通路关键酶的表达及其相关性,明确其在黏膜炎性反应机制中的作用。方法将24例 CRS 患者中鼻甲外侧黏膜按海口分型分期标准分为3组(组1为Ⅰ型2期,组2为Ⅱ型2期,组3为Ⅲ型,每组8例),8例正常鼻黏膜作为对照。应用免疫组化和荧光实时定量多聚酶链反应检测 COX-2、p38丝裂原激活蛋白激酶(p38MAPK)、细胞外信号调节蛋白激酶(ERK)、c-Jun氨基端激酶(JNK)、NF-κB p65和 p50的表达,并分析其相关性。结果 COX-2、p38MAPK、ERK 和NF-κB在3组 CRS 中均有表达,强度高于对照组,差异有统计学意义(P 值均<0.05);3组 CRS 之间表达差异无统计学意义(P 值均>0.05);JNK 在 CRS 各组和对照组中均无阳性表达。相关性分析表明:CRS 各组中 COX-2、p38MAPK、ERK、NF-κB p65及 p50的蛋白质表达量同 mRNA 表达水平呈直线正相关(P 值均<0.05);在同一组 CRS 中 COX-2与 p38MAPK、ERK 的蛋白质和 mRNA 表达呈正相关(P 值均<0.05);CRS 各组中 COX-2表达与 NF-κB p65、p50的核内表达正相关(P<0.05)。结论CRS 中 COX-2表达上调,与上游 p38MAPK、ERK、NF-κB等信号转导通路具有相关性,提示 COX-2在CRS 鼻黏膜炎性反应中可能受后者调节。更多还原

【Abstract】 Objective To detect the expression and correlation of cyclooxygenase 2(COX-2)and key enzymes both of mitogen activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)pathways in middle turbinate mueosa of chronic rhinosinusitis(CRS)and to investigate their roles in CRS pathogenesy. Methods Twenty-four lateral mucosa of CRS middle turbinates were equally divided into 3 groups according to FESS-97Haikou criterion(CRS type Ⅰ stage 2 in group 1,type Ⅱ stage 2 in group 2,and type Ⅲ in group 3),and 8 normal mucosa were enrolled as control.Immunohistochemistry and fluorescent real time quantitative polymerase chain reaction(FQ-RT-PCR)were performed to detect the expression of COX-2, ERK,p38MAPK,JNK and NF-κB subunits.The correlations between cox-2 and MAPK,NF-κB pathway were statistically treated by Pearson test.Results Positive expressions of COX-2,ERK,p38MAPK and NF- KB subunits were detected in CRS groups,which were stronger than those in control group,by immunohistochemistry and FQ-RT-PCR(P<0.05).Statistic difference was not found among CRS groups (P>0.05).Negative expression of JNK was detected in all groups.Significantly positive correlation between protein and RNA expression of COX-2,ERK,p38MAPK and NF-κB subunits in each CRS group was confirmed by Pearson correlation treatment(P<0.05).Significantly positive correlation of protein and RNA expression between COX-2 and ERK,p38MAPK in same CRS group was also founded(P<0.05).The expression of COX-2 and the nucleic expression of NF-κB subunits in same CRS group was proved to be positively correlated(P<0.05).Conclusions Upregulated expression of COX-2 is correlated with upstream ERK,p58MAPK and NF-κB pathway in CRS.It indicates the involvement of ERK,p38MAPK and NF-κB signal transduction pathway in regulation of COX-2 in CRS.更多还原