miR-155对兔鼻窦炎骨质重塑和Notch-1及DLL4的影响  

Effects of miR-155 on Sinus Bone Remodeling and Notch-1 Signaling Pathway and DLL4 in Rabbits with Sinusitis

作　　者：杨志超[1] 于洋[1] 马会梅 朱金源[2] 梁鹏 高小平[1] YANG Zhichao;YU Yang;MA Huimei;ZHU Jinyuan;LIANG Peng;GAO Xiaoping(Otolaryngology Head and Neck Surgery,the General Hospital of Ningxia Medical University,Yinchuan 750004,China;Department of Intensive Medicine,the General Hospital of Ningxia Medical University,Yinchuan 750004,China;Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院耳鼻咽喉头颈外科,银川750004 [2]宁夏医科大学总医院重症医学科,银川750004 [3]宁夏医科大学,银川750004

出　　处：《宁夏医科大学学报》2022年第7期682-688,共7页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2020AAC03409);宁夏医科大学校级项目(XM2019103)。

摘　　要：目的探讨miR-155对鼻窦炎模型兔Notch-1信号通路及鼻窦骨质重塑的影响。方法将32只兔随机分为假手术组、模型组、miR-155 antagomir组、miR-155 antagomir阴性对照组,除假手术组外,其余各组构建鼻窦炎模型。建模同时,药物处理组兔尾静脉注射miR-155 antagomir、miR-155 antagomir阴性对照,假手术组和模型组兔尾静脉注射等量生理盐水,给药结束24 h后对兔鼻部症状进行评分,然后处死,苏木精-伊红(HE)染色法检测各组兔鼻窦黏膜病理变化情况,并进行炎症评分,CT扫描及碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(TRAP)染色检测兔鼻窦骨壁结构骨质重塑活性并进行评分;酶联免疫吸附法(ELISA)检测兔血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、骨保护素(OPG)、核因子κβ受体活化因子配体(RANKL)水平;实时荧光定量PCR检测鼻窦组织中miR-155及Notch信号通路相关因子mRNA水平;采用免疫印迹法检测鼻窦组织中Notch信号通路相关因子蛋白表达。结果与假手术组比较,模型组兔鼻部症状评分、鼻窦黏膜炎症评分,鼻窦骨壁结构骨质重塑活性评分,血清TNF-α、IL-6、OPG及RANKL水平,鼻窦组织miR-155表达水平,Notch-1和DLL4 mRNA及蛋白表达水平均升高(P均<0.05)。与模型组比较,miR-155 antagomir组兔鼻部症状评分,鼻窦黏膜炎症评分,鼻窦骨壁结构骨质重塑活性评分,血清TNF-α、IL-6、OPG及RANKL水平,鼻窦组织miR-155表达水平,Notch-1和DLL4 mRNA及蛋白表达水平均降低(P均<0.05);miR-155antagomir阴性对照组各指标均无明显变化(P均>0.05)。结论下调miR-155表达可抑制Notch-1信号通路激活,降低炎性因子及OPG、RANKL表达,减轻炎性反应,减弱鼻窦骨质重塑,改善鼻窦炎症状。Objective To investigate the effects of mi R-155 on Notch-1 signaling pathway and bone remodeling of paranasal sinuses in sinusitis rabbits model.Methods 32 rabbits were randomly divided into sham operation group,model group,mi R-155 antagomir group and mi R-155 antagomir negative control group.In addition to the sham operation group,the other groups constructed sinusitis model.At the same time,the drug treatment group was injected with mi R-155 antagomir and mi R-155 antagomir negative control through tail vein,while the sham operation group and model group were injected with the same amount of normal saline.After 24 hours of administration,the nasal symptoms were scored,and then the rabbits were killed.The pathological changes of the sinusoid mucosa of each group were detected by hematoxylin eosin staining(HE)and the inflammation score was also made,CT scanning,alkaline phosphatase(ALP)and tartrate resistant acid phosphatase(TRAP)staining were used to detect the bone remodeling activity of the bone wall structure of the nasal sinuses;the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),osteoprotegerin(OPG)and nuclear factor kappa-βreceptor activator ligand(RANKL)were detected by enzyme-linked immunosorbent assay(ELISA);the levels of mi R-155 and Notch signaling pathway related factors m RNA were detected by real-time fluorescent quantitative PCR;Western blot was used to detect the expression of Notch signaling pathway related factors in nasal sinuses.Results Compared with those in the sham operation group,the nasal symptoms score,nasal mucosa inflammation score of paranasal sinuses,bone remodeling activity score of nasal sinus bone wall structure,serum TNF-α,IL-6,OPG and RANKL levels,the expression of mi R-155,the expression levels of Notch-1 and DLL4 m RNA and protein in paranasal sinuses in the model group were significantly higher(P all0.05).Conclusion Downregulating the expression of mi R-155 can inhibit the activation of Notch-1 signaling pathway,reduce the expression of inflammatory factor

关 键 词：MIR-155 鼻窦炎 Notch-1信号通路 鼻窦骨质重塑 

分 类 号：R765.41[医药卫生—耳鼻咽喉科]