目的从环氧合酶2(COX-2)、受激活调节正常T细胞表达和分泌因子(RANTES)及其上游调控因子核因子-κB(NF-κB)的角度探索鼻渊舒口服液(辛夷、苍耳子、薄荷,等)改善鼻窦黏膜炎症持续状态的可能机制。方法 140只雄性C57小鼠均分为正常组、模型组、假手术组、克拉霉素组及鼻渊舒低、中、高剂量组。除正常组及假手术组外,各治疗组小鼠由肺炎链球菌诱导造成慢性鼻-鼻窦炎模型,每日分别给予克拉霉素103 mg/kg,鼻渊舒口服液3.1、6.2、12.4 m L/kg。灌胃2周后,取鼻窦黏膜,HE染色观察黏膜病理状况,实时定量PCR观察COX2、RANTES基因表达,Western blot法检测NF-κBp50表达。结果模型组鼻窦黏膜慢性炎细胞浸润明显,上皮大片脱落,鼻窦黏膜组织病理指数,COX2、RANTES mRNA及NF-κBp50表达较正常及假手术组显著增高。鼻渊舒中、高剂量组黏膜慢性炎细胞浸润较模型组明显减轻,上皮形态完整,鼻窦黏膜组织病理指数显著低于模型组;鼻渊舒中剂量组COX2、RANTES mRNA表达及中、高剂量组NF-κBp50蛋白表达较模型组显著降低。结论鼻渊舒口服液具有抑制慢性鼻-鼻窦炎(CRS)时鼻窦黏膜持续炎症状态的作用,其机制与抑制NF-κB通路、减少COX2、RANTES靶基因表达有关。
AIM To probe the hidden mechanism of Biyuanshu Oral Liquid( Biyuanshu)( Magnoliae Flos,Xanthii Fructus,Methae Herba,et al.) reducing the persistent inflammation of rhinosinusitis from the point of view of cyclooxygenase-2( COX-2),regulated on activation,normal T cell expressed and secreted factor( RANTES)and their upstream regulatory nuclear factor-kappa B( NF-κB). METHODS One hundred and forty male C57 mice were randomly assigned to normal,model,sham operation,clarithromycin groups,low-,medium-,and highdosage Biyuanshu groups. Chronic rhinosinusitis( CRS) was then induced by streptococcus pneumoniae in all groups except the normal and sham operation groups. In drug-treatment groups,mice were given clarithromycin103 mg / kg,Biyuanshu 3. 1 m L / kg,6. 2 m L / kg and 12. 4 m L / kg for two weeks. Nasal sinuses mucosa tissues were gathered to observe pathological alterations by HE dyeing; tissue samples were also used to detect COX2,RANTES gene expression by real-time PCR and NF-κBp50 protein expression by Western blot. RESULTS The model group appeared chronic inflammatory cell infiltration and large falling-off areas,accompanied with higher pathology index scores and increased expressions of COX2,RANTES and NF-κBp50 than in the normal and sham operation groups. Nasal sinuses mucosa in Biyuanshu medium-dosage and high-dosage groups presented less chronic inflammatory cell infiltration and nearly intact epithele. They also showed markedly lower pathology index scores than CRS model group. Compared with the model group,much lower mRNA expressions of COX2,RANTES were detected in Biyuanshu medium-dosage group,and remarkably lower protein expression of NF-κBp50 was observed in Biyuanshu medium-dosage as well as high-dosage groups. CONCLUSION Continued inflammation of nasal sinuses mucosa could be related to high expressions of NF-κBp50 and its downstream target genes such as COX2,RANTES. Based on experimental results,we reckon Biyuanshu to alleviate continuous inflammation occurring in nasal