【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。

【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.