中国血液净化

中国血液净化 ›› 2018, Vol. 17 ›› Issue (05): 299-303.doi: 10.3969/j.issn.1671-4091.2018.05.003

• 临床研究 • 上一篇    下一篇

尿毒症血液透析患者外周血单核细胞Nrf2、NQO1 及血清TNF-α、IL-6的表达变化及意义

胡波1,商义2,李蓓睿1   

  1. 1.攀钢集团总医院肾内科 2. 川北医学院第二附属医院肾内科
  • 收稿日期:2018-02-07 修回日期:2018-03-12 出版日期:2018-05-12 发布日期:2018-05-12
  • 基金资助:

    攀枝花市2015年度市级财政科技专项资金项目(2015CY-S-32)

Expression changes of Nrf2 and NQO1 in peripheral mononuclear cells and TNF-α and IL-6 in serum in uremic hemodialysis patients

  • Received:2018-02-07 Revised:2018-03-12 Online:2018-05-12 Published:2018-05-12

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摘要： 【摘要】目的分析尿毒症血液透析患者外周血单核细胞核因子E2 相关因子2(Nrf2)、醌氧化还原酶(triphosphopyridine nucleotide quinine oxidoreductase，NQO1)及血清肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)、白细胞介素6(interleukin，IL-6)的表达变化及意义。方法选择2015年6 月～2017 年8 月在攀钢集团总医院进行血液透析6 个月以上的46 例尿毒症患者作为透析组，37 例新诊断的尿毒症患者作为未透析组，同时期25 例体检健康者作为健康组对照。分别检测3 组血清TNF-α、IL-6、白蛋白(albumin，Alb)、总胆固醇(total cholesterol，TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterin，LDL-C)及血红蛋白(hemoglobin，Hb)水平，检测单核细胞Nrf2 和NQO1mRNA 和蛋白表达量，分析透析组患者血清TNF-α、IL-6 水平与AIb、TC、LDL-C、Hb 水平及Nrf2、NQO1 相对表达量的关系。结果透析组和未透析组血清TNF-α(t=6.937，P＜0.001；t=8.462，P＜0.001)、IL- 6(t=8.068，P＜0.001；t=8.937，P＜0.001)、TC(t= 2.301, P=0.024；t=4.338, P＜0.001)和LDL-C(t =4.489，P＜0.001；t =7.032，P＜0.001)水平显著高于健康组，血清AIb(t=6.040，P＜0.001；t=4.266，P＜0.001)、Hb水平(t=3.859，P＜0.001；t=2.478，P=0.016)显著低于健康组；透析组血清TNF-α(t=2.205，P=0.030)、IL- 6(t=2.327，P=0.022)、TC(t=2.123，P=0.037)、LDL- C(t=2.106，P=0.038)、Alb(t=2.357，P=0.021)和Hb 水平(t=2.179，P=0.032)显著低于未透析组；透析组和未透析组Nrf2(t=9.525，P＜0.001；t=7.858，P＜0.001)、NQO1(t =7.517，P＜0.001；t=9.046，P＜0.001)mRNA 相对表达量显著低于健康组；透析组Nrf2 (t=2.612，P=0.011)、NQO1(t=2.523，P=0.014)mRNA 相对表达量显著低于未透析组；透析组和未透析组Nrf2(t=7.345，P＜0.001；t=6.107，P＜0.001)、NQO1(t=6.247，P＜0.001；t=7.689，P＜0.001)蛋白表达显著低于健康组，透析组Nrf2(t =2.351，P=0.021)和NQO1(t=2.207，P=0.030)蛋白表达显著低于未透析组。透析组患者血清TNF-α、IL-6 与Alb 呈显著负相关关系(r=-0.672，P＜0.001；r=-0.654，P＜0.001)，与Hb 呈显著负相关关系(r =-0.521，P=0.001；r=-0.537，P＜0.001)，与TC 呈显著正相关关系(r=0.574，P＜0.001；r=0.412，P =0.005)，与LDL-C 呈显著正相关关系(r=0.618，P＜0.001；r=0.622，P＜0.001)；透析组患者血清TNF-α、IL- 6 与Nrf2 相对表达量呈显著负相关(r=- 0.726，P＜0.001；r=- 0.732，P＜0.001)，与NQO1 相对表达量呈显著负相关关系(r=-0.714，P＜0.001；r=-0.721，P＜0.001)；Nrf2 与NQO1相对表达量呈显著正相关(r=0.691，P＜0.001)。结论尿毒症血液透析患者内源性抗氧化能力减弱，机体处于炎症状态，与患者营养不良、脂代谢紊乱及贫血有关。

关键词: 尿毒症血液透析, 外周血单核细胞, 肿瘤坏死因子α, 核因子E2相关因子2, 醌氧化还原酶

Abstract: 【Abstract】Objective To analyze the expression changes of nuclear factor E2 related factor 2 (Nrf2) and quinone oxidoreductase (NQO1) in peripheral mononuclear cells and tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in serum in uremic hemodialysis patients. Methods A total of 46 uremic patients treated with hemodialysis for more than 6 months in our hospital from June 2015 to August 2017 were recruited as the dialysis group, and 37 newly diagnosed uremic patients were enrolled as the non-dialysis group. In addition, 25 healthy subjects were recruited as the healthy group. Hemoglobin (Hb), serum TNF-α, IL-6, albumin (Alb), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and the mRNA and protein levels of Nrf2 and NQO1 in mononuclear cells were assayed. These laboratory results in dialysis group were compared with those in non-dialysis group and healthy group. Results Serum TNF-α, IL-6, TC, and LDL-C were significantly higher in dialysis group and non-dialysis group than in healthy group (For TNF-α, t=6.937, P＜0.001 in dialysis group; t=8.462, P＜0.001 in non- dialysis group. For IL- 6, t=8.068, P＜0.001 in dialysis group; t=8.937, P＜0.001 in non- dialysis group. For TC, t=2.301, P=0.024 in dialysis group; t=4.338, P＜0.001 in non-dialysis group. For LDL-C, t=4.489, P＜0.001 in dialysis group; t=7.032, P＜0.001 in non-dialysis
group). Serum Alb and Hb were significantly lower in dialysis group and non- dialysis group than in healthy group (For Alb, t=6.040, P＜0.001 in dialysis group; t=4.266, P＜0.001 in non- dialysis group. For Hb, t=3.859, P＜0.001 in dialysis group; t=2.478, P=0.016 in non-dialysis group). Serum TNF-α, IL-6, TC,
LDL-C, Alb and Hb were significantly lower in dialysis group than in non- dialysis group (For TNF-α, t=2.205, P=0.030. For IL-6, t=2.327, P=0.022. For TC, t=2.123, P=0.037. For LDL-C, t=2.106, P=0.038. For Alb, t=2.357, P=0.021. For Hb, t=2.179, P=0.032). The relative mRNA levels of Nrf2 and NQO1 in peripheral mononuclear cells were significantly lower in dialysis group and non-dialysis group than in healthy group (For Nrf2, t=9.525, P＜0.001 in dialysis group; t=7.858, P＜0.001 in non-dialysis group. For NQO1, t=7.517, P＜0.001 in dialysis group; t=9.046, P＜0.001 in non-dialysis group), and were significantly lower in dialysis group than in non-dialysis group (For Nrf2, t=2.612, P=0.011. For NQO1, t=2.523, P=0.014). The relative protein levels of Nrf2 and NQO1 in peripheral mononuclear cells were significantly lower in dialysis group and non-dialysis group than in healthy group (For Nrf2, t=7.345, P＜0.001 in dialysis group; t=6.107, P＜0.001 in non- dialysis group. For NQO1, t=6.247, P＜0.001 in dialysis group; t=7.689, P＜0.001 in non- dialysis group), and were significantly lower in dialysis group than in non-dialysis group (For Nrf2, t=2.351, P=0.021. For NQO1, t=2.207, P=0.030). In dialysis group, serum TNF-α and IL-6 were negatively correlated with Alb and Hb (For TNF-α/Alb, r=-0.672, P＜0.001. For IL-6/Alb, r=-0.654, P＜0.001. For TNF-α/Hb, r=-0.521, P=0.001. For IL-6/Hb, r=-0.537, P＜0.001), positively correlated with TC and LDL-C (For TNF-α/TC, r=0.574, P＜0.001. For IL- 6/TC, r=0.412, P=0.005. For TNF- α/LDL- C, r= 0.618, P＜0.001. For IL- 6/LDL- C, r=0.622, P＜0.001), and negatively correlated with the expression of Nrf2 and NQO1 (For TNF- α/ Nrf2, r=-0.726, P＜0.001. For IL-6/ Nrf2, r=-0.732, P＜0.001. For TNF-α/ NQO1, r=-0.714, P＜0.001. For IL-6/ NQO1, r=- 0.721, P＜0.001). In dialysis group, the expression level of Nrf2 was positively correlated with that of NQO1 (r= 0.691, P＜0.001). Conclusion In uremic patients, the endogenous antioxidant capacity
was reduced and the body was in an inflammation status. These abnormalities were resulted from malnutrition, lipid metabolism disturbances and anemia.

Key words: Hemodialysis, Peripheral blood mononuclear cells, Tumor necrosis factor α, Nuclear factor E2 related factor 2, Quinone oxidoreductase