山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (6): 76-82.doi: 10.6040/j.issn.1671-7554.0.2020.105
• • 上一篇
孙文凯1,孙卉2,邬信芳1,高伟3,孟朝暾4,李钦5
SUN Wenkai1, SUN Hui2, WU Xinfang1, GAO Wei3, MENG Zhaotun4, LI Qin5
摘要: 目的 通过检测自噬标志物Beclin-1和P62与增殖因子Ki67在鼻息肉的蒂部及体部的表达及其相关性,探讨自噬与增殖在鼻息肉发展过程中的作用及其机制。 方法 收集2018年7月至2019年5月于临沂市人民医院行手术治疗的46例慢性鼻窦炎伴鼻息肉(CRSwNP)患者的息肉组织作为实验组(分为2个亚组:蒂部组与体部组),另取10例鼻中隔偏曲患者的正常鼻中隔黏膜组织作为对照组。苏木精-伊红(HE)染色并根据鼻息肉组织中嗜酸性粒细胞浸润情况对实验组进行病理分型;免疫组织化学技术法(IHC)检测Beclin-1、P62和Ki67在鼻息肉蒂部、体部及对照组中的蛋白表达情况; Western blotting检测Beclin-1和P62蛋白在3组中的表达;Spearman秩和相关分析法分析鼻息肉组织中Beclin-1、P62和Ki67三者之间的表达相关性。 结果 Beclin-1、P62和Ki67的表达与鼻息肉的病理分型无明显关联(P均>0.05)。Beclin-1在鼻息肉蒂部中的表达强度较体部明显降低,且与对照组比较均降低,差异有统计学意义(H=71.835,P<0.05);P62在鼻息肉蒂部中的表达较体部则明显升高,且与对照组比较均升高,差异有统计学意义 (H=74.666,P<0.05);Ki67在鼻息肉蒂部中的表达较体部则明显升高,且两者与对照组比较均升高,差异有统计学意义(H=76.716,P<0.05)。Beclin-1与P62的表达呈负相关关系(rs=-0.674,P<0.05);Ki67 与Beclin-1表达呈负相关关系(rs=-0.640,P<0.05);Ki67与P62的表达呈正相关关系(rs=0.708,P<0.05)。 结论 自噬标志物Beclin-1和P62与增殖因子Ki67在鼻息肉组织蒂部与体部之间的表达存在差异,并且三者之间的相关性分析表明鼻息肉中自噬与增殖存在负相关关系。鼻息肉蒂部中自噬的活性相对较低而增殖活性相对较高,可能促进了鼻息肉的发生发展。
中图分类号:
[1] Levine B, Kroemer G. Autophagy in the pathogenesis of disease[J]. Cell, 2008, 132(1): 27-42. [2] Chen JY, Hour TC, Yang SF, et al. Autophagy is deficient in nasal polyps: implications for the pathogenesis of the disease[J]. Int Forum Allergy Rhinol, 2015, 5(2): 119-123. [3] Ye Y, Zhao J, Ye J, et al. The role of autophagy in the overexpression of MUC5AC in patients with chronic rhinosinusitis[J]. Int Immunopharmacol, 2019, 71: 169-180. doi:10.1016/j.intimp.2019.03.028. [4] Shun CT, Lin SK, Hong CY, et al.Sirtuin 6 modulates hypoxia-induced autophagy in nasal polyp fibroblasts via inhibition of glycolysis[J]. Am J Rhinol Allergy, 2016, 30(3): 179-185. [5] Wang LF, Chien CY, Yang YH, et al. Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism[J]. Rhinology, 2015, 53(3): 270-276. [6] Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists[J]. Rhinology, 2012, 50(1): 1-12. [7] Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: focus on nasal polyposis[J]. Allergy Clin Immunol, 2015, 136(6): 1431-1440. [8] Wang BF, Cao PP, Wang ZC, et al. Interferon-gamma-induced insufficient autophagy contributes to p62-dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps[J]. Allergy, 2017, 72(9): 1384-1397. [9] 齐君君. 自噬相关基因Beclin1及P62在鼻息肉组织中的表达及临床意义[D]. 济南: 山东大学, 2016. [10] Luo Q, Zhang J, Wang H, et al. Expression and regulation of transcription factor foxA2 in chronic rhinosinusitis with and without nasal polyps[J]. Allergy Asthma Immunol Res, 2015, 7(5): 458-466. [11] Shi JB, Fu QL, Zhang H, et al. Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities[J]. Allergy, 2015, 70(5): 533-539. [12] DeConde AS, Mace JC, Levy JM, et al. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis[J]. Laryngoscope, 2017, 127(3): 550-555. [13] 马进, 刘毅. 自噬标志基因Beclin1和p62在变应性鼻炎中的表达及临床意义[J]. 中国耳鼻咽喉颅底外科杂志, 2019, 25(6): 600-605. MA Jin, LIU Yi. Expression and clinical significance of autophagy marker genes Beclin1and p62in allergic rhinitis[J]. Chinese Journal of Otorhinolaryngology-Skull Base Surgery, 2019, 25(6): 600-605. [14] Jiang X, Fang L, Wu H, et al. TLR2 Regulates allergic airway inflammation and autophagy through PI3K/Akt signaling pathway[J]. Inflammation, 2017, 40(4): 1382-1392. [15] 张金陵, 蔡晓岚, 李学忠, 等. 自噬相关基因Atg3、Ambra1与慢性单纯性鼻窦炎、鼻息肉及鼻息肉伴发哮喘的相关性研究[J]. 山东大学耳鼻喉眼学报, 2016, 30(2): 50-55. ZHANG Jinling, CAI Xiaolan, LI Xuezhong, et al. Study of autophagy-related genes atg3, ambral expressions in chronic rhinosinusitis without or with nasal polyps accompanied with asthma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2016, 30(2): 50-55. [16] 齐君君,韩学锋,蔡晓岚,等. 自噬相关基因Beclin1及P62在鼻息肉中的表达及临床意义[J]. 中华耳鼻咽喉头颈外科杂志, 2016, 51(6): 428-432. QI Junjun, HAN Xuefeng, CAI Xiaolan, et al. Expression and clinical significance of autophagy-related gene Beclinl and P62 in nasal polyps[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2016, 51(6): 428-432. [17] Brown DC, Gatter KC. Ki67 protein: the immaculate deception?[J]. Histopathology, 2002, 40(1): 2-11. [18] Ambhore NS, Katragadda R, Raju Kalidhindi RS, et al. Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation[J]. Mol Cell Endocrinol, 2018, 476: 37-47. doi: 10.1016/j.mce.2018.04.007. [19] Hu M, Tang Y, Long G, et al. Primary extracranial meningioma of mastoid in a patient with history of skin squamous cell carcinoma, lung adenocarcinoma and prostatic carcinoma[J]. Anticancer Res, 2019, 39(6): 3197-3201. [20] Tezer I, Celebi Erdivanli O, Sanli A, et al. Could cellular proliferation be a predictive index for the relapse of nasal polyposis and down-regulated by nasal steroid treatment?[J]. Indian J Otolaryngol Head Neck Surg, 2013, 65(Suppl 2): 329-332. [21] Kosem M, Bulut G, Kaya Z. Analysis of Ki-67 immunoreactivity in recurring and nonrecurring nasal polyps[J]. J Otolaryngol Head Neck Surg, 2010, 39(4): 464-467. [22] Zhao L, Li YY, Li CW, et al. Increase of poorly proliferated p63(+)/Ki67(+)basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps[J]. Allergy, 2017, 72(6): 975-984. [23] 王哲, 王佳贺. 小白菊内酯对人甲状腺癌细胞BCPAP增殖及自噬的影响[J]. 现代肿瘤医学, 2019, 27(22): 3939-3943. WANG Zhe, WANG Jiahe. The influence of parthenolide on proliferation and autophagy of human thyroid carcinoma cell line BCPAP[J]. Journal of Modern Oncology, 2019, 27(22): 3939-3943. [24] 张帆, 燕太强, 郭卫. Rasfonin抑制骨肉瘤细胞143B的增殖和迁移[J]. 北京大学学报(医学版), 2019, 51(2): 234-238. ZHANG Fan, YAN Taiqiang, GUO Wei. Rasfonin inhibits proliferation and migration of osteosarcoma 143B cells[J]. Journal of Peking University(Health Sciences), 2019, 51(2): 234-238. [25] 关红卫,李娟,孙锐,等. 乌苯美司对卵巢癌A2780细胞的生物学影响[J]. 山东大学学报(医学版), 2019, 57(12): 46-51. GUAN Hongwei, LI Juan, SUN Rui, et al. Biological effects of ubenimex on ovarian cancer A2780 cell[J]. Journal of Shandong University(Health Sciences), 2019, 57(12): 46-51. [26] Yang LY, Li X, Li WT, et al. Vgamma1(+)gammadeltaT cells are correlated with increasing expression of eosinophil cationic protein and metalloproteinase-7 in chronic rhinosinusitis with nasal polyps inducing the formation of edema[J]. Allergy Asthma Immunol Res, 2017, 9(2): 142-151. [27] Tecimer SH, Kasapoglu F, Demir UL, et al. Correlation between clinical findings and eosinophil/neutrophil ratio in patients with nasal polyps[J]. Eur Arch Otorhinolaryngol, 2015, 272(4): 915-921. [28] Simsek F, Eren E, Bahceci S, et al. High PI3K/mTOR and low MAPK/JNK activity results in decreased apoptosis and autophagy in nasal polyposis[J]. Braz J Otorhinolaryngol, 2020, pii: S1808-8694(20)30006-9. doi:10.1016/j.bjorl.2019.12.005. |
[1] | 陈泉材,韩赛,刘露,孙雨,尤学武,张俊华,张友忠. CDC7、MCM4在105例宫颈病变组织中的表达及意义[J]. 山东大学学报 (医学版), 2022, 60(1): 34-39. |
[2] | 徐兵,李勇,刘明,刘永辉. 沉默PRRX1基因表达可增强前列腺癌耐药细胞株PC-3/DTX对多西他赛的敏感性[J]. 山东大学学报 (医学版), 2021, 59(6): 103-110. |
[3] | 张华宇,殷思源,刘健,马嘉旭,宋茹,曹国起,王一兵. 氧糖剥夺条件下培养表皮干细胞的定量蛋白质组学分析[J]. 山东大学学报 (医学版), 2021, 59(4): 17-27. |
[4] | 张小红,周云,杜秋莹,任慧欣,王超群. Atg7-siRNA通过调节精氨酸循环干扰食管癌ECA109细胞放疗敏感性[J]. 山东大学学报 (医学版), 2021, 59(4): 28-34. |
[5] | 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1-6. |
[6] | 孙盼盼,赵旭,林小雯,傅志俭. 医用臭氧对大鼠骨关节炎软骨细胞中PPARγ及自噬水平表达的影响[J]. 山东大学学报 (医学版), 2020, 58(6): 14-21. |
[7] | 孙红林,韩波,王静,高聆,朱梅,姜殿东,吕建利. CD40siRNA调控c-Jun氨基末端激酶对自身免疫性心肌炎大鼠心肌细胞自噬的影响[J]. 山东大学学报 (医学版), 2019, 57(4): 9-14. |
[8] | 熊超,刘力,冯建国,魏继承. 七氟醚预处理对H9C2心肌细胞缺氧/复氧后转录沉默信息调节器3的表达及乙酰化水平的影响[J]. 山东大学学报 (医学版), 2019, 57(3): 25-30. |
[9] | 关红卫,李娟,孙锐,刘婕,李长忠. 乌苯美司对卵巢癌A2780细胞的生物学影响[J]. 山东大学学报 (医学版), 2019, 57(12): 46-51. |
[10] | 蒿魁元,赵圣,张宇,崔迪,荆翌峰,夏术阶,韩邦旻. 雄激素阻断对膀胱癌UM-UC-3细胞自噬与凋亡的影响[J]. 山东大学学报 (医学版), 2018, 56(3): 41-47. |
[11] | 赵姗姗,李晓梅,梁婷,张超,宋静,侯桂华. 自噬对125I-anti-TLR5同种移植排斥靶向显像的影响[J]. 山东大学学报(医学版), 2017, 55(9): 46-52. |
[12] | 殷雷,殷睿,李文佳,刘帅,吕家驹. CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性[J]. 山东大学学报(医学版), 2017, 55(8): 1-6. |
[13] | 任宝鑫,马云峰,刘殿伟,李卓,姜勇. Wnt3a在大鼠蛛网膜下腔出血后早期脑损伤中对神经细胞自噬和凋亡的影响[J]. 山东大学学报(医学版), 2016, 54(10): 11-15. |
[14] | 黄智龙, 刘帅, 王建伟, 韩立平, 王晓庆, 李新, 毕东滨, 解放, 牛志宏. 乌苯美司诱导肾癌细胞死亡的作用及机制[J]. 山东大学学报(医学版), 2015, 53(9): 58-64. |
[15] | 赵雪莲, 于君, 谢兆宏, 曹彦军, 刘震, 王晓, 徐琳琳, 杨慧, 郑晓磊, 沈阳, 毕建忠. 线粒体自噬在阿尔茨海默病细胞模型中的作用机制[J]. 山东大学学报(医学版), 2015, 53(10): 1-5. |
|