吉林大学学报(医学版) ›› 2021, Vol. 47 ›› Issue (5): 1209-1214.doi: 10.13481/j.1671-587X.20210518

• 基础研究 • 上一篇    下一篇

N-乙酰半胱氨酸对高尿酸血症大鼠氧化应激和血管内皮功能的影响及其机制

王兴华,杨洪娟,胡秀红,崔红蕊,徐保振,李丹露,王涛,高玉伟()   

  1. 河北医科大学第一医院中西医结合肾内科,河北 石家庄 050031
  • 收稿日期:2021-01-13 出版日期:2021-09-28 发布日期:2021-10-26
  • 通讯作者: 高玉伟 E-mail:ckqc8629@163. com
  • 作者简介:王兴华(1981-),男,河北省石家庄市人,主治医师,医学硕士,主要从事中西医结合诊治肾脏疾病方面的研究。
  • 基金资助:
    河北省卫健委医学科学研究课题计划项目(20190466)

Effects of N-acetyl-L-cysteine on oxidative stress and vascular endothelial function in rats with hyperuricemia and their mechanisms

Xinghua WANG,Hongjuan YANG,Xiuhong HU,Hongrei CUI,Baozhen XU,Danlu LI,Tao WANG,Yuwei GAO()   

  1. Department of Nephrology of Integrated Traditional Chinese and Western Medicine,First Hospital,Hebei Medical University,Shijiazhuang 050031,China
  • Received:2021-01-13 Online:2021-09-28 Published:2021-10-26
  • Contact: Yuwei GAO E-mail:ckqc8629@163. com

摘要: 目的

探讨N-乙酰半胱氨酸(NAC)对高尿酸血症(HUA)大鼠氧化应激和血管内皮功能的影响,并阐明其作用机制。

方法

将60只SD大鼠随机分为对照组、模型组、低剂量NAC组和高剂量NAC组,每组15只。除对照组外,其他各组均采用氧嗪酸钾灌胃法建立HUA大鼠模型。低和高剂量NAC组大鼠分别给予75和300 mg·kg-1 NAC灌胃处理,对照组和模型组大鼠给予等量生理盐水灌胃,每天1次,连续干预4周。腹主动脉取血并分离血清,检测各组大鼠血清尿酸(UA)、血尿素氮(BUN)、血肌酐(Scr)、内皮素1(ET-1)、一氧化氮(NO)水平及氧化应激指标总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性以及丙二醛(MDA)水平;免疫组织化学法检测各组大鼠胸主动脉组织中内皮型一氧化氮合成酶(eNOS)表达水平。

结果

与对照组比较,模型组大鼠血清中UA、MDA和ET-1水平明显升高(P<0.05),血清中T-SOD、CAT和GSH-Px活性及NO水平明显降低(P<0.05),胸主动脉组织中eNOS表达水平明显降低(P<0.05),而血清中BUN和Scr水平差异无统计学意义(P>0.05)。与模型组比较,高剂量NAC组大鼠血清中UA、MDA和ET-1水平明显降低(P<0.05),血清中T-SOD、CAT和GSH-Px活性及NO水平以及胸主动脉组织中eNOS表达水平均明显升高(P<0.05),血清中BUN和Scr水平差异无统计学意义(P>0.05),而低剂量NAC组大鼠以上各指标差异无统计学意义(P>0.05)。与低剂量NAC组比较,高剂量NAC组大鼠血清中UA、MDA和ET-1水平明显降低(P<0.05),血清中T-SOD、CAT和GSH-Px活性及NO水平以及胸主动脉组织中eNOS表达水平均明显升高(P<0.05),血清中BUN和Scr水平差异无统计学意义(P>0.05)。

结论

NAC可降低HUA大鼠血清中UA水平,减轻其体内氧化应激水平,改善血管内皮功能。

关键词: N-乙酰半胱氨酸, 高尿酸血症, 氧化应激, 血管内皮功能

Abstract: Objective

To investigate the effects of N-acetyl-L-cysteine (NAC) on the oxidative stress and vascular endothelial function in the rats with hyperuricemia (HUA), and to elucidate their mechanisms.

Methods

Totally 60 SD rats were randomly divided into control group, model group, low dose of NAC group and high dose of NAC group,with 15 rats in each group. Except for control group, the rats in all other groups were administered with potassium oxonate to induce the HUA models. The rats in low and high doses of NAC groups were given 75 and 300 mg·kg-1 NAC respectively by gavage, while the rats in control group and model group were given the same amount of normal saline, once a day for 4 weeks. The blood samples of rats were collected from abdominal aorta and the serum was separated. The levels of serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), endoderin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA), and the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured. The expression levels of endothelial nitric oxide synthase (eNOS) in thoracic aorta tissue of the rats in various groups were detected by immunohistochemistry method.

Results

Compared with control group, the levels of UA, MDA and ET-1 of the rats in model group were obviously increased (P<0.05), the activities of serum T-SOD, CAT and GSH-Px, the level of NO and the expression level of eNOS in thoracic aorta tissue were significantly decreased (P<0.05), while there were no statistical differences in the levels of serum BUN and Scr (P>0.05). Compared with model group, the levels of serum UA, MDA and ET-1 in high dose of NAC group were significantly decreased (P<0.05), the activities of serum T-SOD, CAT, and GSH-Px, the level of NO and the expression level of eNOS in thoracic aorta tissue were markedly increased (P<0.05), while there were no statistical differences in the levels of serum BUN and Scr (P>0.05); there were no statistical differences in the changes of the above indexes in low dose of NAC group (P>0.05). Compared with low dose of NAC group, the levels of serum UA, MDA and ET-1 of the rats in high dose of NAC group were significantly decreased (P<0.05), the activities of serum T-SOD, CAT, and GSH-Px, the level of NO and the expression level of eNOS in thoracic aorta tissue were markedly increased (P<0.05),while there were no statistical differences in the levels of serum BUN and Scr (P>0.05).

Conclusion

NAC can decrease the level of serum UA in the HUA rats, reduce the level of oxidative stress in the body, and improve the vascular endothelial function.

Key words: N-acetyl-L-cysteine, hyperuricemia, oxidative stress, vascular endothelial function

中图分类号: 

  • R589.7