浏览全部资源
扫码关注微信
尿毒症毒素对甲酚对人冠状动脉内皮细胞氧化应激的影响
Effects of uremic toxin p-cresol on oxidative stress in human coronary artery endothelial cells
- 第三军医大学学报 2021年43卷第16期 页码：1543-1549
- 作者机构：
1.541001 广西 桂林，桂林医学院附属医院肾内科
2.541001 广西 桂林，中国人民解放军联勤保障部队第九二四医院心内科
3.400038 重庆，陆军军医大学(第三军医大学)第二附属医院肾内科
- 作者简介：
[李小励，E-mail: lxl55358@163.comLI Xiaoli, E-mail: lxl55358@163.com
- 基金信息：广西自然科学基金面上项目(2018GXNSFAA138119)
DOI：10.16016/j.1000-5404.202102059
中图分类号： R322.121;R329.25;R914.4收稿：2021-02-28，
修回：2021-03-30，
纸质出版：2021-08-30
- 稿件说明：
移动端阅览
李莉, 李静, 袁发焕, 等. 尿毒症毒素对甲酚对人冠状动脉内皮细胞氧化应激的影响[J]. 第三军医大学学报, 2021,43(16):1543-1549.
Li LI, Jing LI, Fahuan YUAN, et al. Effects of uremic toxin p-cresol on oxidative stress in human coronary artery endothelial cells[J]. Journal of Third Military Medical University, 2021, 43(16): 1543-1549.
李莉, 李静, 袁发焕, 等. 尿毒症毒素对甲酚对人冠状动脉内皮细胞氧化应激的影响[J]. 第三军医大学学报, 2021,43(16):1543-1549. DOI： 10.16016/j.1000-5404.202102059.
Li LI, Jing LI, Fahuan YUAN, et al. Effects of uremic toxin p-cresol on oxidative stress in human coronary artery endothelial cells[J]. Journal of Third Military Medical University, 2021, 43(16): 1543-1549. DOI： 10.16016/j.1000-5404.202102059.
摘要
目的
2
探讨尿毒症毒素对甲酚对人冠状动脉内皮细胞(human coronary artery endothelial cells
HCAECs)氧化应激的影响。
方法
2
体外培养HCAECs，将不同浓度的游离对甲酚或者不同浓度与4%白蛋白结合的对甲酚，分别作用HCAECs 24、48 h，采用MTT检测各组细胞增殖，特异性ELISA试剂盒检测细胞活性氧自由基(reactive oxygen species，ROS)水平，实时定量聚合酶链反应(real-time PCR)检测细胞中还原型烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate oxidase，NADPH)氧化酶NOX2和NOX4的mRNA表达，Western blot检测细胞中NOX2、NOX4、p-p38和p-38的蛋白表达。
结果
2
游离的和蛋白结合的对甲酚显著抑制HCAECs的增殖(
P
＜0.05)，增加HCAECs中ROS的含量(
P
＜0.05)、NOX2、NOX4 mRNA表达(
P
＜0.05)和NOX2、NOX4、p-p38蛋白表达(
P
＜0.05)。
结论
2
游离的和蛋白结合的对甲酚通过调控MAPKs信号通路诱导HCAECs氧化应激，抑制HCAECs增殖。
Abstract
Objective
2
To investigate the effects of uremic toxin p-cresol (PC) on the oxidative stress of human coronary artery endothelial cells (HCAECs).
Methods
2
HCAECs were cultured
in vitro
and treated with different concentrations of free PC alone or combined with 4% albumin for 24 and 48 h
respectively. Cell proliferation was detected by MTT assay; The production of cellular reactive oxygen free radicals (reactive oxygen species
ROS) was detected with specific ELISA kit; The mRNA levels of NADPH oxidases NOX2 and NOX4 were measured with real-time PCR; The protein levels of NOX2
NOX4
p-p38 and p-38 were tested with Western blotting.
Results
2
Free and protein-bound PC significantly inhibited the proliferation of HCAECs (
P
<
0.05)
increased the production of ROS (
P
<
0.05)
enhanced the mRNA expression levels of NOX2 and NOX4 (
P
<
0.05)
and up-regulated the protein levels of NOX2
NOX4 and p-p38 in HCAECs (
P
<
0.05).
Conclusion
2
The free and protein-bound PC induces oxidative stress and inhibits the proliferation of HCAECs by regulating the MAPKs signaling pathway.
关键词
Keywords
references
DEO A, SCHMID C H, EARLEY A, et al . Loss to analysis in randomized controlled trials in CKD[J ] . Am J Kidney Dis, 2011, 58(3): 349-355. DOI: 10.1053/j.ajkd.2011.04.023.
REISS A B, MIYAWAKI N, MOON J, et al . CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies[J ] . Atherosclerosis, 2018, 278: 49-59. DOI: 10.1016/j.atherosclerosis.2018.08.046.
CLARK W R, DEHGHANI N L, NARSIMHAN V, et al . Uremic toxins and their relation to dialysis efficacy[J ] . Blood Purif, 2019, 48(4): 299-314. DOI: 10.1159/000502331.
GOMÓȽKA M, NIEMCZYK L, SZAMOTULSKA K, et al . Protein-bound solute clearance during hemodialysis[J ] . Adv Exp Med Biol, 2019, 1153: 69-77. DOI: 10.1007/5584_2019_336.
DOU L, BERTRAND E, CERINI C, et al . The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair[J ] . Kidney International, 2004, 65: 442-451. DOI: 10.1111/j.1523-1755.2004.00399.x.
JOURDE-CHICHE N, DOU L, SABATIER F, et al . Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients[J ] . J Thromb Haemost, 2009, 7(9): 1576-1584. DOI: 10.1111/j.1538-7836.2009.03540.x.
FENG B, ZHANG Y, MU J, et al . Preventive effect of a proteasome inhibitor on the formation of accelerated atherosclerosis in rabbits with uremia[J ] . J Cardiovasc Pharmacol, 2010, 55(2): 129-138. DOI: 10.1097/FJC.0b013e3181c87f8e.
FENG B, ZHANG Y Q, MU J, et al . Uraemic serum induces dysfunction of vascular endothelial cells: role of ubiquitin-proteasome pathway[J ] . Exp Physiol, 2011, 96(8): 801-815. DOI: 10.1113/expphysiol.2011.058149.
MU J, FENG B, YE Z, et al . Visfatin is related to lipid dysregulation, endothelial dysfunction and atherosclerosis in patients with chronic kidney disease[J ] . J Nephrol, 2011, 24(2): 177-184. DOI: 10.5301/jn.2010.3488.
JANSEN J, JANKOWSKI J, GAJJALA P R, et al . Disposition and clinical implications of protein-bound uremic toxins[J ] . Clin Sci Lond Engl, 2017, 131(14): 1631-1647. DOI: 10.1042/CS20160191.
GRYP T, VANHOLDER R, VANEECHOUTTE M, et al . p-Cresyl Sulfate[J ] . Toxins, 2017, 9(2): 52. DOI: 10.3390/toxins9020052.
李莉, 光丽霞, 王代红, 等. 对甲酚对人脐静脉内皮细胞增殖和细胞周期的影响[J]. 中华肾脏病杂志, 2013(9): 676-680. DOI: 10.3760/cma.j.issn.1001-7097.2013.09.007.
LI L, GUANG L X, WANG D H, et al . Effects of p-cresol on the proliferation and cell cycle of human umbilical vein endothelial cells[J ] . Chin J Nephrol, 2013(9): 676-680. DOI: 10.3760/cma.j.issn.1001-7097.2013.09.007.
LI L, LI J, LI X, et al . Protein-bound P-cresol inhibits human umbilical vein endothelial cell proliferation by inducing cell cycle arrest at G0/G1[J ] . Am J Transl Res, 2017, 9(4): 2013-2023.
ATHERTON J G, HAINS D S, BISSLER J, et al . Generation, clearance, toxicity, and monitoring possibilities of unaccounted uremic toxins for improved dialysis prescriptions[J ] . Am J Physiol Ren Physiol, 2018, 315(4): F890-F902. DOI: 10.1152/ajprenal.00106.2017.
INCALZA M A, D'ORIA R, NATALICCHIO A, et al . Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases[J ] . Vascul Pharmac ol, 2018, 100: 1-19. DOI: 10.1016/j.vph.2017.05.005.
ZHANG Y, MURUGESAN P, HUANG K, et al . NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets[J ] . Nat Rev Cardiol, 2020, 17(3): 170-194. DOI: 10.1038/s41569-019-0260-8.
SUN H J, WU Z Y, NIE X W, et al . Role of endothelial dysfunction in cardiovascular diseases: the link between inflammation and hydrogen sulfide[J ] . Front Pharmacol, 2019, 10: 1568. DOI: 10.3389/fphar.2019.01568.
YUE J, LOPEZ J M. Understanding MAPK signaling pathways in apoptosis[J]. Int J Mol Sci, 2020, 21(7): 2346. DOI: 10.3390/ijms21072346.
TANAKA K, HONDA M, TAKABATAKE T. Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte[J]. J Am Coll Cardiol, 2001, 37(2): 676-685. DOI: 10.1016/s0735-1097(00)01123-2.
MCCUBREY J A, LAHAIR M M, FRANKLIN R A. Reactive oxygen species-induced activation of the MAPkinase signaling pathways[J]. Antioxid Redox Signal, 2006, 8(9/10): 1775-1789. DOI: 10.1089/ars.2006.8.1775.
BARRETO F C, BARRETO D V, LIABEUF S, et al . Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients[J ] . Clin J Am Soc Nephrol, 2009, 4(10): 1551-1558. DOI: 10.2215/cjn.03980609.
0
浏览量
0
下载量
0
CSCD
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
