紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及SIRT1/Nrf2信号通路的影响

Effects of shikonin on inflammatory response and SIRT1/Nrf2 signaling pathway of nasal mucosa in mice with chronic rhinosinusitis

目的研究紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及沉默信息调控因子1(SIRT1)/核因子E2相关因子2(Nrf2)信号通路的影响。方法选取80只小鼠建立慢性鼻窦炎模型后随机分为模型组,紫草素12.5、50.0 mg/kg组,克拉霉素组,每组20只。另取正常饲养的20只小鼠设为假手术组。各组小鼠分别ig给予相应药物,1次/d,共14 d。采用苏木素–伊红(HE)染色观察小鼠鼻黏膜组织病理形态学;Masson染色观察小鼠鼻黏膜组织胶原沉积情况;ELISA法检测小鼠血清中炎性因子水平;Western blotting实验检测小鼠鼻黏膜组织中SIRT1/Nrf2信号通路相关蛋白表达。结果与模型组比较,紫草素12.5、50.0 mg/kg组小鼠鼻窦黏膜慢性炎症表现和蓝色胶原沉积明显改善;血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-32(IL-32)、γ干扰素(IFN-γ)水平显著降低;鼻黏膜组织中SIRT1、Nrf2、血红素氧合酶-1(HO-1)、NADPH醌氧化还原酶1(NQO-1)蛋白表达水平显著升高(P<0.05)。且紫草素50.0 mg/kg组小鼠上述指标均显著优于紫草素12.5 mg/kg组(P<0.05)。结论紫草素能够改善慢性鼻窦炎小鼠鼻黏膜组织重塑和炎症反应,其作用机制可能与激活SIRT1/Nrf2信号通路有关。

Objective To study the effects of shikonin on the inflammatory response of nasal mucosa and silent information regulator 1(SIRT1)/nuclear factor E2-related factor 2(Nrf2)signaling pathway in mice with chronic rhinosinusitis.Methods Eighty mice were selected to establish chronic sinusitis model and were randomly divided into model group,shiksin 12.5,50.0 mg/kg group,and clarithromycin group,with 20 mice in each group.Another 20 mice in normal feeding were selected as sham operation group.Each group was given the corresponding drug intragastrically,once daily,for 14 days.The pathological morphology of mice nasal mucosa was observed by HE staining,collagen deposition in mice nasal mucosa was observed by Masson staining,the level of inflammatory factors in mice serum were detected by ELISA method,and the expression of SIRT1/Nrf2 signaling pathway related proteins in mice nasal mucosa were detected by Western blotting.Results Compared with model group group,the chronic inflammation and blue collagen deposition of nasal sinuses mucosa in shikonin 12.5 and 50.0 mg/kg group were significantly improved,the levels of TNF-α,IL-32,and IFN-γin serum were decreased,and the expression levels of SIRT1,Nrf2,HO-1,and NQO-1 protein in nasal mucosa were increased(P<0.05).The above indexes of mice in shikonin 50.0 mg/kg group were significantly better than those in shikonin 12.5 mg/kg group(P<0.05).Conclusion Shikonin can improve the tissue remodeling and inflammatory response of nasal mucosa in chronic rhinosinusitis,and its mechanism may be related to the activation of SIRT1/Nrf2 signaling pathway.