慢性鼻-鼻窦炎鼻黏膜中糖原合成酶激酶3β与PI3K／Akt及白细胞介素6间的相关性

Relationship among the expression of GSK3β, PDK/Akt, and IL-6 in chronic rhinosinusitis

目的研究慢性鼻-鼻窦炎鼻黏膜中糖原合成酶激酶3B（glycogensynthasekinase313，GSK3p）与P13K／Akt信号通路以及细胞因子白细胞介素（intedeukin，IL）6之间的相关性及其意义。方法分别用半定量反转录聚合酶链反应（RT—PCR）、免疫组化法检测30例慢性鼻一鼻窦炎伴鼻息肉（chronicrhinosinusitiswithnasalpolyps，CRSwNP）患者、20例慢性鼻-鼻窦炎不伴鼻息肉（chronicrhinosinusitiswithoutnasalpolyps，CRSsNP）患者的组织标本以及20例鼻中隔偏曲患者的鼻黏膜标本中GSK313、P13K、Akt的mRNA和蛋白质的表达，并用半定量RT—PCR检测细胞因子IL-6在CRSwNP组、CRSsNP组和对照组鼻黏膜中的表达。采用SPSS16．0软件进行统计学分析。结果GSK313、P13K、Akt、IL-6mRNA在CRSwNP组中的相对表达量分别为0．6254±0．0584、0．8239±0．7186、0．9369±0．0823、0．8973±0．0680，在对照组分别为0．2684±0．0726、0．3578±0．0994、0．6721±0．0590、0．5898±0．0891，差异有统计学意义（t值分别为2．358、3．071、2．764、2．239，P值均〈0．05）。以上四项指标在CRSwNP组和CRSsNP组之间的表达差异无统计学意义（t值分别为1．597、1．842、1．468、0．926，P值均〉0．05）。GSK3B、P13K、Akt蛋白主要表达在黏膜上皮细胞、黏膜下腺体细胞及炎性细胞中，阳性染色主要定位于胞质，其在CRS鼻黏膜中的阳性表达率明显高于对照组中的阳性表达率，差异有统计学意义（x。值分别为16．42、16．25、15．57，P值均〈0．01）。GSK313、P13K、Akt蛋白在CRSwNP组和CRSsNP组的阳性表达率差异无统计学意义（x2值分别为3．27、2．85、2．46，P值均〉0．05）。GSK3B与P13K、Akt以及IL-6在CRS患者中的表达呈正相关趋势（r值分别为0．645、0．617、0．583，P值均〈0．01）。结论IL-6、P13K、Akt、GSK3B在CRS鼻黏膜中的异常表达可能在CRS的发生、发展过程中发挥着一定的作用。

Objective To explore the relationship among the expression of GSK3β, PI3K/Akt signaling transduction pathway, and cytokines IL-6 in chronic rhinosinusitis. Methods The mRNA and protein for GSK3β, PI3K, Akt were assayed by using reverse transcription polymerase chain reactoin （RT- PCR） and immunohistochemistry （IHC）, and the cytokines IL-6 mRNA measured by using reverse transcription polymerase chain reactoin （RT-PCR） in the nasal tissue from the patients with chronic rhinosinusitis with nasal polyps （CRSwNP）, chronic rhinosinusitis without nasal polyps （CRSsNP） and control subjects. SPSS 16. 0 software was used to analyze the data. Results The relative expression levels of GSK3 β, PI3 K, Akt and IL-6 in CRSwNP were 0. 6254 ± 0. 0584, 0. 8239± 0.7 186, 0. 9369 ±0.0823 and 0. 8973 ±0. 0680. But the relative expression levels of GSK3, PI3K, Akt and IL-6 in control subjects were 0.2684 ± 0. 0726, 0. 3578 ± 0. 0994, 0. 6721± 0. 0590, 0. 5898 ± 0. 0891. There were significant differences between the groups of CRSwNP and control subjects（t values were 2. 358, 3. 071, 2. 764, and 2. 239, respectively, all P 〈0.05）. There was no significant difference of GSK3~, PI3K ,Akt and GSK3β between the groups of CRSwNP and CRSsNP （t values were 1. 597, 1. 842, 1. 468 and 0. 926 , respectively , all P 〈0.05）. GSK3β, PI3K , Akt were not only expressed in the cytoplasm of the epithelium and gland cells, but also in the cytoplasm of the inflammatory cell. GSK3β, PI3K, Akt protein in CRS were deteced at a higher rate than the normal nasal tissue （X2 values were 16.42, 16.25 and 15.57, respectively, all P 〈 0. 01 ）. However there was no significant difference of GSK3β, PI3K, Akt protein between the groups of CRSwNP and CRSsNP （ X2 values were 3.27, 2.85 and 2.46, respectively, all P 〉 0.05 ）. There was a positive correlation trend among the expression of GSK3β, PI3K, Akt and IL-6 in CRS （r values were 0. 645, 0.617 and 0. 583, respectively, all P 〈 0.01 ）. Conclusion The abnormal expression of IL-6, PI3K, Akt and GSK3β in the nasal mucosa of CRS may play a pro-inflammatory role in the occurrence and development of CRS.