摘要
目的探究牡荆素对变应性鼻炎大鼠鼻黏膜损伤的保护作用及其调控机制。方法将SD大鼠随机分为对照组、模型组、牡荆素(3、6、12 mg/kg),及牡荆素(12 mg/kg)+EX527(5 mg/kg)组,每组各10只。除对照组外,其余各组大鼠均采用卵清白蛋白诱导建立变应性鼻炎大鼠模型,模型构建成功后,各组大鼠ip相应剂量药物,对照组和模型组大鼠ip等量的生理盐水,1次/d,连续14 d。末次给药结束后30 min,记录各组大鼠行为学评分,观察鼻黏膜组织病理形态学变化;检测鼻黏膜组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、丙二醛(MDA)、活性氧气簇(ROS)、铁离子(Fe^(2+))水平,铁死亡相关蛋白溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合成酶长链家族成员4(ACSL4)以及沉默信息调节因子1(Sirt1)、叉头框蛋白O1(FoxO1)、p-FoxO1、Ac-FoxO1蛋白表达。结果与模型组相比,牡荆素各剂量组大鼠行为学评分均显著降低,鼻黏膜损伤显著改善(P<0.05);大鼠鼻黏膜组织匀浆SOD、GSH活性显著升高,MDA、ROS、Fe^(2+)含量均显著降低(P<0.05);大鼠鼻黏膜组织SLC7A11、GPX4、Sirt1、FoxO1蛋白表达显著升高,p-FoxO1、Ac-FoxO1、ACSL4蛋白表达显著降低(P<0.05),且呈剂量相关性。结论牡荆素能够改善变应性鼻炎大鼠鼻黏膜损伤,其机制与激活鼻黏膜组织Sirt1/FoxO1通路,抑制细胞铁死亡有关。
Objective To investigate the protective effect and regulatory mechanism of vitexin on nasal mucosal damage with allergic rhinitis in rats.Methods SD rats were randomly divided into control group,model group,vitexin(3,6,and 12 mg/kg)group,and vitexin(12 mg/kg)+EX527(5 mg/kg)with 10 rats in each group.Except for the control group,all other groups of rats were induced with ovalbumin to establish a rat model of allergic rhinitis.After the successful establishment of the model,the rats in each group were ip administered with the corresponding dose of drugs,and the rats in the control group and the model group were ip administered with the same amount of normal saline once daily for 14 consecutive days.30 Minutes after the end of the last administration,record the behavioral scores of rats in each group and observe the pathological and morphological changes of nasal mucosa tissue.Detect the levels of SOD,GSH,MDA,ROS,and Fe^(2+)in nasal mucosa tissue,as well as the expression of ferroptosis related proteins SLC7A11,GPX4,ACSL4,Sirt1,FoxO1,p-FoxO1,and Ac-FoxO1 proteins.Results Compared with model group,the behavioral scores of rats in vitexin groups were significantly decreased,and the nasal mucosa injury was significantly improved(P<0.05).The activities of SOD and GSH in rat nasal mucosa homogenate were significantly increased,while the contents of MDA,ROS and Fe^(2+)were significantly decreased(P<0.05).The protein expressions of SLC7A11,GPX4,Sirt1,and Fox O1 in rat nasal mucosa were significantly increased,while the protein expressions of p-FoxO1,Ac-FoxO1,and ACSL4 were significantly decreased(P<0.05),and were dose-dependent.Conclusion Vitexin can improve nasal mucosal damage in allergic rhinitis rats,and its mechanism is related to activating the Sirt1/FoxO1 pathway and inhibiting ferroptosis in nasal mucosal tissue.
作者
李艳峰
卢振民
LI Yanfeng;LU Zhenmin(Department of Otolaryngology,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453100,China)
出处
《现代药物与临床》
CAS
2024年第1期14-22,共9页
Drugs & Clinic
基金
河南省高等学校重点科研项目(20B320117)。
