高糖通过Nox4型NADPH氧化酶影响施旺细胞凋亡的机制研究*

doi:10.12047/j.cjap.5719.2019.029

中国应用生理学杂志 ›› 2019, Vol. 35 ›› Issue (2): 130-134.doi: 10.12047/j.cjap.5719.2019.029

高糖通过Nox4型NADPH氧化酶影响施旺细胞凋亡的机制研究^*

于婷¹,辛青¹,许飞²,李雷^3△

1. 济宁医学院基础医学院生理学教研室, 山东济宁 272067;
2. 济宁市第一人民医院血管外科, 山东济宁 272011;
3. 济宁医学院附属医院神经内四科, 山东济宁 272029

出版日期:2019-03-28 发布日期:2019-06-27
通讯作者: Tel: 18678746862; E-mail: iampolkers@163.com
基金资助:
济宁市科技助推新旧动能转换计划资助课题(2017SMNS004);济宁市科技发展计划项目(2014jnyx05);济宁医学院青年教师科研扶持基金(JY2016KJ023Y)

Research on the mechanism of high glucose affecting the apoptosis of schwann cells by Nox4 NADPH oxidase

YU Ting¹ , XIN Qing¹ , XU Fei², LI Lei^3△

1. Department of Physiology, Jining Medical University, Jining 272067;
2. Department of Vascular Surgery, Jining First People's Hospital, Jining 272011;
3. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272029, China

Online:2019-03-28 Published:2019-06-27

摘要/Abstract

摘要： 目的: 探讨高糖通过Nox4型NADPH氧化酶影响施旺细胞凋亡的机制。方法: 提取Wistar大鼠新生鼠的施旺细胞体外培养。分为对照组、高糖组、NOX4 siRNA组及对照siRNA组(n=10)。采用WST-1法检测细胞活力,DCFH-DA法检测细胞内活性氧自由基(ROS)含量,荧光实时定量 RT-PCR检测Nox4和Caspase3 mRNA表达,蛋白印迹法检测Nox4和Caspase3蛋白表达。结果: 高糖培养上调施旺细胞Nox4 mRNA及蛋白表达,降低施旺细胞活性,增加细胞内ROS含量,通过增加Caspase3 mRNA及蛋白表达促进细胞凋亡。NOX4 siRNA通过抑制Nox4基因表达,阻止高糖培养的施旺细胞内ROS蓄积,降低高糖对施旺细胞的活性损害,通过下调Caspase3 mRNA及蛋白表达减少细胞凋亡。结论: Nox4参与高糖引起的施旺细胞凋亡,针对Nox4表达或功能的调控方式可能成为治疗糖尿病周围神经病变的新途径。

关键词: 糖尿病, 施旺细胞, NADPH氧化酶, 活性氧自由基, 凋亡

Abstract: Objective: To investigate the mechanism of high glucose affecting the apoptosis of schwann cells through Nox4 NADPH oxidase. Methods: The schwann cells of newborn Wistar rats were cultured in vitro. The cultured cells were divided into four groups: control group, high-glucose group, NOX4 siRNA group and control siRNA group (n=10). The WST-1 method was used to detect the cell vitality, and the DCFH-DA method was used to detect the contents of intracellular reactive oxygen free radicals (ROS). Nox4 and Caspase3 mRNA expressions were detected by real-time fluorescence quantitative RT-PCR. Nox4 and Caspase3 protein expressions were determined by Western blot. Results: High glucose culture up-regulated Nox4 mRNA and protein expressions of schwann cells, decreased activity of schwann cells, increased intracellular ROS content, and promoted apoptosis by increasing Caspase3 mRNA and protein expressions. NOX4 siRNA blocked the accumulation of ROS in the high glucose cultured schwann cells, and reduced the damage of glucose on cell viability, by inhibiting NOX4 gene expression. NOX4 siRNA also reduced cell apoptosis by down-regulating Caspase3 mRNA and protein expressions. Conclusion: Nox4 was involved in the hyperglycemic-induced apoptosis of schwann cells through ROS. The regulation of Nox4 expression or function might be a new way to treat diabetic peripheral neuropathy.

Key words: diabetes, schwann cells, NADPH oxidase, reactive oxygen free radicals, apoptosis

于婷, 辛青, 许飞, 李雷. 高糖通过Nox4型NADPH氧化酶影响施旺细胞凋亡的机制研究^*[J]. 中国应用生理学杂志, 2019, 35(2): 130-134.

YU Ting , XIN Qing , XU Fei, LI Lei. Research on the mechanism of high glucose affecting the apoptosis of schwann cells by Nox4 NADPH oxidase[J]. CJAP, 2019, 35(2): 130-134.

参考文献

[1] Feldman EL, Nave KA, Jensen TS, et al. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain[J]. Neuron, 2017, 93(6): 1296-1313.
[2] Yu T, Li L, Bi Y, et al. Erythropoietin attenuates oxidative stress and apoptosis in Schwann cells isolated from streptozotocin-induced diabetic rats [J]. J Pharm Pharmacol, 2014, 66(8): 1150-1160.
[3] 陈娟, 崔节达, 郭晓桐, 等. 慢性阻塞性肺疾病小气道 NOX4、TGF -β的表达与气道重塑的关系[J]. 中国应用生理学杂志, 2017, 33(6): 481-487.
[4] Nisimoto Y, Diebold BA, Cosentino-Gomes D, et al. Nox4: a hydrogen peroxide-generating oxygen sensor [J]. Biochemistry, 2014, 53(31): 5111-5120.
[5] Gon alves NP, V gter CB, Pallesen LT. Peripheral glial cells in the development of diabetic neuropathy [J]. Front Neurol, 2018, 9: 268.
[6] 马益梅, 李传达, 朱雅冰, 等. RvD1对大鼠2型糖尿病神经病理性痛的作用及机制研究[J]. 中国应用生理学杂志, 2017, 33(3), 277-281.
[7] Lennertz RC, Medler KA, Bain JL, et al. Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy [J]. J Neurophysiol, 2011, 106(2): 905-914.
[8] Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, et al. Cellular death, reactive oxygen species (ROS) and diabetic complications [J]. Cell Death Dis, 2018, 9(2): 119.
[9] Zhang L, Pang S, Deng B, et al. High glucose induces renal mesangial cell proliferation and fibronectin expression through JNK/NF-κB/NADPH oxidase/ROS pathway, which is inhibited by resveratrol [J]. Int J Biochem Cell Biol, 2012, 44(4): 629-638.
[10]何婷. 白藜芦醇抑制糖尿病肾病肾间质纤维化的作用和机制研究 [D]. 重庆: 第三军医大学, 2015: 75-76.
[11]Rozentsvit A, Vinokur K, Samuel S, et al. Ellagic acid reduces high glucose-induced vascular oxidative stress through ERK1/2/NOX4 signaling pathway [J]. Cell Physiol Biochem, 2017, 44(3): 1174-1187.
[12]Li Q, Lin Y, Wang S, et al. GLP-1 inhibits high-glucose-induced oxidative injury of vascular endothelial cells [J]. Sci Rep, 2017, 7(1): 8008.
[13]Yao M, Cao F, Wang X, et al. Nox4 is involved in high glucose-induced apoptosis in renal tubular epithelial cells via Notch pathway [J]. Mol Med Rep, 2017, 15(6): 4319-4325.
[14]Hou Q, Lei M, Hu K, et al. The effects of high glucose levels on reactive oxygen species-induced apoptosis and involved signaling in human vascular endothelial cells [J]. Cardiovasc Toxicol, 2015, 15(2): 140-146.
[15]Jha JC, Gray SP, Barit D, et al. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy [J]. J Am Soc Nephrol, 2014, 25(6): 1237-1254.

高糖通过Nox4型NADPH氧化酶影响施旺细胞凋亡的机制研究^*

Research on the mechanism of high glucose affecting the apoptosis of schwann cells by Nox4 NADPH oxidase

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

[1]	扈敬, 李法东, 邵小婷, 李思葳, 张欣颖, 赵冰冰, 徐长庆, 魏璨. 精胺对高糖引起的大鼠心肌纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 193-196.
[2]	朱建忠, 赵灿, 隋月林, 刘媛媛, 乔跃兵. 瘦素对糖尿病大鼠糖脂代谢及炎性因子的影响[J]. 中国应用生理学杂志, 2020, 36(3): 197-201.
[3]	孙晓娟, 冯武龙, 侯娜, 李娜, 姜蔚丽. 有氧运动和白藜芦醇对2型糖尿病大鼠肾脏JAK2及TGF-β1的影响[J]. 中国应用生理学杂志, 2020, 36(3): 202-206.
[4]	邵小婷, 扈敬, 张欣颖, 赵冰冰, 李思葳, 高萍, 徐长庆, 魏璨. 外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 207-210.
[5]	刘凯丽, 都新新, 张文琴, 吴亚俐, 王茜, 王春芳, 崔香丽. 过表达miR-31对结肠炎模型小鼠TLR4/NF-κB信号通路及凋亡蛋白的调控[J]. 中国应用生理学杂志, 2020, 36(3): 211-215.
[6]	陈宇峰, 董凡赫, 楼云玮, 寿今豪, 张慧婷, 周一超, 严明, 毛红娇, 张云. 补骨脂素对TCP磨损颗粒所致大鼠成骨细胞损伤的干预作用及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 255-260.
[7]	霍海燕, 王瑾, 张许梅, 张文婷, 岳继萍, 焦向英. 糖尿病诱导硫氧还蛋白相互作用蛋白(TXNIP)对小鼠胰岛β细胞衰老的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 119-123.
[8]	计红, 邵子益, 薛琳琳, 牛春阳, 詹雪龙, 杨闯, 甄莉, 杨焕民, 李士泽. α-烯醇化酶基因干扰表达对籽鹅卵泡颗粒细胞增殖及凋亡的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 184-188.
[9]	邵毅英, 范玉琪, 李思葳, 赵冰冰, 邵小婷, 扈敬, 徐长庆, 魏璨. CaSR表达在大鼠糖尿病性肝硬化损伤和纤维化发生中的作用[J]. 中国应用生理学杂志, 2020, 36(1): 1-5.
[10]	衣雪洁, 孙玉霞, 姚婷婷, 李晶, 高畅, 刘璐, 曹师承, 常波, 张翠萍. 急、慢性运动对2型糖尿病大鼠脂肪PI3K/AKT/GLUT4通路的影响[J]. 中国应用生理学杂志, 2020, 36(1): 12-16.
[11]	刘姣, 周刚, 梅雨, 谢文杰, 李鹏飞, 杨帆. 一次性力竭运动致大鼠骨骼肌氧化应激的机制[J]. 中国应用生理学杂志, 2020, 36(1): 17-22.
[12]	彭志锋, 张继红, 杨德兵. 早期跑步运动对大鼠脑缺血/再灌注损伤后神经行为与神经元凋亡的影响[J]. 中国应用生理学杂志, 2020, 36(1): 39-41.
[13]	包晓辰, 方以群, 马骏, 王芳芳. 依达拉奉对小鼠肺型氧中毒的保护作用及其机制[J]. 中国应用生理学杂志, 2020, 36(1): 73-76.
[14]	周海涛, 曹建民, 胡戈, 张静, 郭娴, 牛衍龙, 王安琪, 杜堃, 魏江山, 关云鹏, 邵芙蓉, 赵卓. 姜黄素对过度训练致大鼠脾脏细胞凋亡的调控作用及其机制^*[J]. 中国应用生理学杂志, 2019, 35(6): 501-505.
[15]	杨子键, 黄君瑶, 高烨飞, 黄文吉, 徐世磊, 金晶晶, 万烨东, 严明, 毛红娇, 张云. 佛手苷内酯对磷酸三钙磨损颗粒诱导骨细胞损伤的影响及机制^*[J]. 中国应用生理学杂志, 2019, 35(6): 563-568.