>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
PURα介导糖尿病神经病变大鼠发病神经元中p27kip-1和TNF-α的表达及其意义
作者:闵静  何婷  王莉  唐莎  付莎莉  徐子辉 
单位:华中科技大学同济医学院附属武汉中心医院 内分泌科, 湖北 武汉 430000
关键词:糖尿病神经病变 人转录因子活性蛋白α p27kip-1 肿瘤坏死因子α 大鼠 转染 
分类号:R587.2;R-33
出版年·卷·期(页码):2019·38·第三期(427-432)
摘要:

目的:探讨人转录因子活性蛋白α(PURα)介导糖尿病神经病变(DN)神经元中抑制蛋白p27kip-1和肿瘤坏死因子α(TNF-α)的表达及其意义。方法:采用腹膜腔注射链脲佐菌素法制备DN大鼠作为DN组,以健康大鼠为对照组,每组20只。比较1周内两组大鼠病理性疼痛和热痛觉过敏情况,分析两组大鼠背根节(DRG)神经元PURα、p27kip-1和TNF-α的表达。取鼠源海马神经元细胞株HT-22,转染为4组:PURα过表达组(转染PURα表达质粒)、mock组(不转染任何表达载体)、空白对照组(转染空表达载体)及PURα沉默组(转染PURαRNAi表达质粒),分析细胞株PURα、p27kip-1和TNF-α的表达。结果:与对照组比较,DN组大鼠出现明显的触觉异常性疼痛和热痛觉过敏(P<0.05),DN组大鼠DRG神经元PURα、p27kip-1及TNF-α的表达上调(P<0.05),PURα与p27kip-1及TNF-α的表达呈显著正相关(P<0.05)。神经元细胞株中上调PURα的表达能显著提高p27kip-1及TNF-α的表达水平(P<0.05),抑制细胞内源PURα表达,p27kip-1及TNFα的表达水平则显著降低(P<0.05)。结论:PURα可介导p27kip-1和TNF-α蛋白表达,可能参与了DN的发病过程。

Objective:To explore the purine-rich element binding protein alpha(PURα)-mediated expression of p27kip-1and tumor necrosis factor alpha(TNF-α) in the pathogenesis of diabetic neuropathy(DN). Methods:DN rats were prepared by intraperitoneal injection of streptozotocin as the DN group, and healthy rats were used as the control group with 20 rats in each group. The pathological pain and thermal hyperalgesia were compared between the two groups within one week. The expression levels of PURα, p27kip-1 and TNF-α in dorsal root ganglion(DRG) neurons in the two groups were analyzed by Western blot. The mouse hippocampal neuron cell line HT-22 was transfected into 4 groups,i.e., the PURα overexpression group (transfected with PURα expression plasmid), the mock group(without transfection of any expression vector),the blank control group (transfected empty expression vector) and the PURα silencing group (transfected with PURα RNAi expression plasmid), and the expression of PURα, p27kip-1 and TNF-α in the four cell lines groups were determined. Results:Compared with the control group, the tactile allodynia and thermal hyperalgesia were increased,and the expression levels of PURα, p27kip-1 and TNF-α was up-regulated in DRG neurons of the DN group(P<0.05). PURα was significantly and positively correlated with the expression of p27kip-1 and TNF-α(P<0.05). Up-regulation of PURα expression in neuronal cell lines significantly increased the expression of p27kip-1 and TNF-α(P<0.05).As the expression of endogenous PURα was inhibited, the expression levels of p27kip-1 and TNF-α were significantly decreased(P<0.05). Conclusion:PURα can mediate the expression of p27kip-1 and TNF-α protein, which may be involved in the pathogenesis of DN.

参考文献:

[1] 刘文捷,郭曲练,何万友,等.钙稳态调节蛋白1在痛性糖尿病神经病变大鼠脊髓背角的表达变化[J].中国现代医学杂志,2015,25(17):16-21.
[2] MENICHELLA D M,ABDELHAK B,REN D,et al.CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy[J].Mol Pain,2014,10(7):42-47.
[3] 尹代婵,宋俊华,何霞,等.血浆超敏C反应蛋白和同型半胱氨酸水平与2型糖尿病周围神经病变的相关性研究[J].中国现代医学杂志,2015,25(19):64-66.
[4] KOU Z Z,LI C Y,HU J C,et al.Alterations in the neural circuits from peripheral afferents to the spinal cord:possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats[J].Front Neural Circuits,2014,8(1):6-11.
[5] 史平平,傅松波,韦性丽,等.糖尿病神经病变的诊断方法[J].中国老年学杂志,2014,34(18):5327-5329.
[6] ALJ O,HWANG S M,SCARPA J,et al.CaV3.2 T-type calcium channels in peripheral sensory neurons a re important for mibefradil-induced reversal of hyperalgesia and allodynia in rats with painful diabetic Neuropathy[J].PLoS One,2014,9(4):e91467.
[7] 张漫,张绍平,王萌萌,等.Purα促进海马神经元中p27kip-1的表达[J].宁夏医科大学学报,2015,37(12):1384-1387.
[8] 刘强,孙涛,杨征,等.Purα对匹罗卡品致痫大鼠海马DNA损伤的保护作用[J].中华医学杂志,2015,95(27):2214-2218.
[9] LIU H,BARR S M,CHU C,et al.Functional interaction of Pur alpha with the Cdk2 moiety of cyclin A/Cdk2[J].Biochem Biophys Res Commun,2005,328(4):851-857.
[10] 杨征,王峰,袁聪聪,等.Purɑ对癫痫大鼠行为学及海马神经元Caspase-3表达的影响[J].宁夏医科大学学报,2016,38(2):137-140.
[11] 陈天华.Notch1与TLR4信号通路在糖尿病神经病变发病机制中的相互作用[D].济南:山东大学,2016.
[12] 倪桂莲,崔融,陈干明,等.糖尿病大鼠背根神经节JNK的表达水平对足部皮肤组织学变化的影响[J].中国病理生理杂志,2015,31(3):415-420.
[13] HUANG Y,YING Z,ZHOU L,et al.The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy[J].Neurochem,2014,75(9):112-119.
[14] 王晓莉,滕玲,徐丹,等.脂肪源性干细胞移植对糖尿病周围神经病大鼠坐骨神经TNF-α和MBP表达的影响[J].解剖科学进展,2014(4):312-314.
[15] FREY E,VALAKH V,KARNEY-GROBE S,et al.An in vitro assay to study induction of the regenerative state in sensory neurons[J].Exp Neurol,2015,263(1):350-363.
[16] XU D,WANG D,CUI M,et al.The purine-rich element-binding protein ChPur-α negatively regulates Hsc70 transcription in Crassostrea hongkongensis[J].Cell Stress Chaperones,2018,23(1):91-100.
[17] JEANNOT P,CALLOT C,BAER R,et al.Loss of p27Kip-promotes metaplasia in the pancreas via the regulation of Sox9 expression[J].Oncotarget,2015,6(34):35880-35892.
[18] 张漫,张绍平,王萌萌,等.Purα促进海马神经元中p27~(kip-1)的表达[J].宁夏医科大学学报,2015,37(12):1384-1387.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 175411 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364