自噬在肾间质纤维化小鼠中的表达趋势

doi:10.12092/j.issn.1009-2501.2019.03.004

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (3): 260-265.doi: 10.12092/j.issn.1009-2501.2019.03.004

自噬在肾间质纤维化小鼠中的表达趋势

陈薪薪¹，陈宇²，郑尘非¹，周莹¹，陈朝生¹

¹温州医科大学附属第一医院肾内科，温州 325000，浙江；²温州市中医院肾内科，温州 325000, 浙江

收稿日期:2018-10-08 修回日期:2018-12-30 出版日期:2019-03-26 发布日期:2019-04-01
通讯作者: 陈朝生，男，硕士，主任医师，研究方向：肾脏疾病。 Tel:13857756102 E-mail: wzccs8@163.com
作者简介:陈薪薪，女，博士，主治医师，研究方向：肾脏疾病。 Tel:13968830932 E-mail: cxx001166@163.com
基金资助:
浙江省自然科学基金（LY16H150007）；浙江省科技计划项目（2016C33214）；浙江省医药卫生科技项目一般研究项目（2016KYB188）；温州市科技计划项目（Y20160311）

Expression trend of autophagy in mice with renal interstitial fibrosis

CHEN Xinxin ¹, CHEN Yu², ZHENG Chenfei¹, ZHOU Ying ¹, CHEN Chaosheng¹

¹The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China; ²Wenzhou Traditional Chinese Medical Hospital, Wenzhou 325000, Zhejiang, China

Received:2018-10-08 Revised:2018-12-30 Online:2019-03-26 Published:2019-04-01

摘要/Abstract

摘要：

目的: 观察肾间质纤维化单侧输尿管梗阻模型（UUO）术后不同时间点自噬的表达趋势。方法: 32只清洁级健康雄性ICR小鼠随机分组：假手术（Sham）组、UUO模型（UUO）组，分别在 UUO术后 3、7、14 d 处死小鼠，假手术组7 d处死，每组小鼠8只。留取血清检测血肌酐（Scr）、尿素氮（BUN），肾组织行HE和Masson染色，观察光镜病理结果，电镜超微结构观察自噬体的形成，Westernblot检测肾组织LC3蛋白和P62蛋白的表达。结果: UUO术后梗阻侧肾脏皮质变薄，小管萎缩，间质纤维化，单个核细胞浸润，肾小球无明显病变，病理变化以UUO术后14 d最突出。与Sham组相比，LC3-Ⅱ蛋白含量从3 d开始逐渐增高，7 d时达峰值，14 d时下降；而P62与LC3-Ⅱ相反，3 d开始下降，7 d达最低值，14 d又逐渐恢复，表明自噬在7 d这个时间点表达最显著。电镜显示UUO术后7 d出现自噬小体和吞噬泡现象。结论: UUO术后自噬的表达有一定的时间依赖性，在7 d时表达最显著，自噬与病理严重程度不平行。

关键词: UUO, 自噬, LC3-Ⅱ, P62

Abstract:

AIM: To observe the expression trend of autophagy at different time points after UUO surgery. METHODS: Thirty-two clean healthy male ICR mice were randomized into Sham operation (Sham) group and UUO model (UUO) group, and mice were sacrificed at 3, 7 and 14 d after UUO surgery, respectively, 8 mice for each group. Serum was collected to detect Scr, BUN, HE and Masson staining ways were applied to the renal tissue, and the formation of autophagosomes was observed by electron microscopy and the expression of LC3 protein and P62 protein in renal tissue was detected by Westernblot. RESULTS:The renal cortex thinned, tubule atrophy, interstitial fibrosis, single nuclear cell infiltration, no obvious glomerular lesions were found in the obstructed side of UUO postoperatively, and the pathological changes were most prominent on 14 d after UUO surgery. Compared with the Sham group, LC3-Ⅱbegan from 3 d, peaked on 7 d, down on 14 d; P62 was different, 3 d began to decline, 7 d reached the lowest, 14 d recovered gradually, which showed that autophagy was most significant at 7 d. Electron microscopy showed that autophagosome and phagocytic vacuoles appeared 7 days after UUO surgery.CONCLUSION: The expression of autophagy after UUO surgery had a certain time dependence, which was most significant at 7 d, and the severity of autophagy was not parallel to the pathological severity.

Key words: UUO, autophagy, LC3-Ⅱ, P62

中图分类号:

R965.2

陈薪薪，陈宇，郑尘非，周莹，陈朝生. 自噬在肾间质纤维化小鼠中的表达趋势[J]. 中国临床药理学与治疗学, 2019, 24(3): 260-265.

CHEN Xinxin, CHEN Yu, ZHENG Chenfei, ZHOU Ying, CHEN Chaosheng. Expression trend of autophagy in mice with renal interstitial fibrosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 260-265.

参考文献

［1］Eddy AA. Molecular basis of renal fibrosis［J］. Pediatr Nephrol, 2000,15(3/4):290-301.
［2］Khwaja A,El Kossi M,Floege J,et al. The management of CKD: a look into the future［J］.Kidney Int, 2007，72(11):1316-1323.
［3］Ban CR,Twigg SM. Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers［J］. Vasc Health Risk Manag, 2008，4(3):575-596.
［4］Levine B, Kroemer G. Autophagy in the pathogenesis of disease［J］. Cell, 2008,132(1):27-42.
［5］王欣, 陈宝强, 李红玉. 哺乳动物细胞自噬关键节点及相关药物的研究进展［J］. 中国临床药理学与治疗学, 2018，23(2):205-210.
［6］李金玉, 黄丹梅, 张艳美, 等. 巨噬细胞移动抑制因子通过调控自噬抗H9c2心肌细胞缺氧/复氧损伤［J］. 中国临床药理学与治疗学, 2018，23(5):531-535.
［7］Chen Q, Yu S, Zhang K, et al. Exogenous H2S inhibits autophagy in unilateral ureteral obstruction mouse renal tubule cells by regulating the ROS-AMPK signaling pathway［J］. Cell Physiol Biochem, 2018，49(6):2200-2213.
［8］Yan Q, Song Y, Zhang L, et al. Autophagy activation contributes to lipid accumulation in tubular epithelial cells during kidney fibrosis［J］. Cell Death Discov, 2018，27;5:2.
［9］Du C, Ren Y, Yao F, et al. Sphingosine kinase 1 protects renal tubular epithelial cells from renal fibrosis via induction of autophagy［J］. Int J Biochem Cell Biol, 2017，90:17-28.
［10］Zhan X, Yan C, Chen Y, et al.Celastrol antagonizes high glucose-evoked podocyte injury, inflammation and insulin resistance by restoring the HO-1-mediated autophagy pathway［J］. Mol Immunol, 2018，104:61-68.
［11］Chen X, Tong H, Chen Y, et al. Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy［J］. Onco Targets Ther, 2018,11:867-881.
［12］Wang Z, Divanyan A, Jourd'heuil FL, et al. Vimentin expression is required for the development of EMT-related renal fibrosis followingunilateral ureteral obstruction in mice［J］. Am J Physiol Renal Physiol, 2018，315(4):F769-780.
［13］赵燕云, 吴小燕, 汪国敏,等.苯那普利干预Wnt信号通路抑制UUO大鼠肾纤维化的实验研究［J］. 中国临床药理学与治疗学, 2017，22(12):1332-1339.
［14］Havasi A, Zheng D. Autophagy and Tubular Cell Death in the Kidney［J］. Semin Nephrol, 2016,36(3):174-88.
［15］Xu YF, Ruan SW, Wu XN, et al. Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress［J］. Int J Mol Med, 2013, 31(3):628-636.
［16］Xu Y, Yang S, Huang J, et al. Tgf-beta1 induces autophagy and promotes apoptosis in renal tubular epithelial cells［J］. Int J Mol Med, 2012, 29(5): 781-790.
［17］He L, Livingston MJ, Dong Z, et al. Autophagy in acute kidney injury and repair［J］. Nephron Clin Pract, 2014, 127(1/4): 56-60.
［18］Ding Y, Kim SL, Lee SY, et al. Autophagy Regulates TGF-β expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction［J］. J Am Soc Nephrol, 2014, 25(12): 2835-2846.
［19］Kim SI, Na HJ, Ding Y, et al. Autophagy promotes intracellular degradation of type Ⅰ collagen induced by transforming growth factor (TGF)-β1［J］. J Biol Chem, 2012, 287(15): 11677-11688.
［20］Kim WY, Nam SA, Song HC, et al. The role of autophagy in unilateral ureteral obstruction rat model［J］. Nephrology, 2012, 17(2): 148-159.

[1]	王洁, 李龙, 陈凤, 刘胜菲. 核因子E2相关因子2在肺纤维化中的研究进展[J]. 中国临床药理学与治疗学, 2023, 28(9): 1067-1072.
[2]	封壮壮, 宋瑞平, 豆鹏程, 陈心怡, 左娇娇, 舒劲. 基于mTOR/Beclin1/LC3信号轴探讨制萎扶胃丸对胃癌前病变大鼠胃窦组织自噬的影响[J]. 中国临床药理学与治疗学, 2023, 28(4): 361-370.
[3]	白佳, 杨虹, 李玲玲, 张洋洋, 杨莹, 吕海宏. 维生素D通过线粒体/自噬途径影响糖尿病神经病变机制的研究[J]. 中国临床药理学与治疗学, 2023, 28(2): 214-219.
[4]	王洁, 李龙, 陈凤, 刘胜菲. 二甲双胍干预肺纤维化发病机制的研究进展[J]. 中国临床药理学与治疗学, 2023, 28(2): 235-240.
[5]	李菲, 丁慧琴, 陈梦静. 异莲心碱激活ERK信号通路诱导肺癌PC9细胞自噬的作用研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1235-1240.
[6]	张晶玉, 王一涵, 李珺, 金平, 申希平, 王迎斌, 刘婕婷. 自噬促进大鼠肠缺血再灌注损伤的细胞铁死亡[J]. 中国临床药理学与治疗学, 2023, 28(1): 36-41.
[7]	周欢, 徐铭, 李波, 刘春英, 王淳. PI3K/Akt/FOXO3a信号通路介导的保护性自噬参与肺腺癌获得性顺铂耐药表型重塑[J]. 中国临床药理学与治疗学, 2022, 27(9): 961-970.
[8]	张伟, 王迎斌, 曹璐, 刘艳, 张丽, 刘婕婷. 自噬在肠缺血再灌注损伤中的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(9): 1061-1066.
[9]	王珍, 全海燕, 洪陈亮, 袁李佳龙, 秦旭平. 游泳运动通过促进自噬改善糖尿病小鼠肾功能的研究[J]. 中国临床药理学与治疗学, 2022, 27(6): 632-638.
[10]	李雪恒, 李龙. 褪黑素与特发性肺纤维化关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 715-720.
[11]	曹颖. 自噬与炎症性肠病关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(3): 345-352.
[12]	全海燕, 江兴, 何璐. 线粒体自噬在肝胰岛素抵抗中作用机制的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(2): 198-204.
[13]	杨永康, 李静, 饶廷彩, 张骏艳. 金丝桃苷通过调节自噬水平减轻心肌梗死小鼠心脏及胸主动脉的损伤[J]. 中国临床药理学与治疗学, 2021, 26(6): 601-608.
[14]	崔华, 燕红霞, 尹梅. 下调lncRNA LINC00176对肺癌A549/DDP细胞顺铂耐药和自噬的影响[J]. 中国临床药理学与治疗学, 2021, 26(6): 616-623.
[15]	吴畏, 李广鹏, 张江波, 孔令宇, 蔡君艳, 杨飞云. 天麻素联合地塞米松保护缺糖缺氧诱导的H9C2细胞损伤[J]. 中国临床药理学与治疗学, 2021, 26(11): 1244-1249.

自噬在肾间质纤维化小鼠中的表达趋势

Expression trend of autophagy in mice with renal interstitial fibrosis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价