慢性鼻-鼻窦炎中鼻甲黏膜环氧合酶2与上游丝裂原激活蛋白激酶及核因子κB信号通路相关性探讨

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KB（nuclear factor kappaB，NF-KB）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-KBp65和p50的表达，并分析其相关性。结果COX-2、p38MAPK、ERK和NF-KB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050的蛋白质表达量同mRNA表达水平呈直线正相关（P值均〈O．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。

Correlation of cyclooxygenase 2 with upstream mitogen-activated protein kinase, nuclear factor kappa B signal transduction pathway in middle turbinate mucosa of chronic rhinosinusitis

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-KB) pathways in middle turbinate mucosa 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-97 Haikou 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-kappaB subunits. The correlations between cox-2 and MAPK, NF-kappaB pathway were statistically treated by Pearson test. RESULTS: Positive expressions of COX-2, ERK, p38MAPK and NF-kappaB 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-kappaB 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-kappaB 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, p38MAPK and NF-kappaB pathway in CRS. It indicates the involvement of ERK, p38MAPK and NF-kappaB signal transduction pathway in regulation of COX-2 in CRS.