Protection effect of nicorandil against acute kidney injury induced by contrast agent in elderly patients with AMI after PCI
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摘要: 目的 探究尼可地尔对老年急性心肌梗死(acute myocardial infarction，AMI)患者经皮冠状动脉介入治疗(percutaneous coronary intervention，PCI)术后造影剂诱导急性肾损伤的保护作用。方法 选取2019年9月—2021年10月住院行PCI术的老年AMI患者141例，随机分为对照组、尼可地尔低剂量组和尼可地尔高剂量组，每组47例；对照组患者接受常规治疗方案(阿司匹林+氯吡格雷+水化治疗)，尼可地尔低剂量组和尼可地尔高剂量组在对照组基础上，术前30 min至术后3 d服用尼可地尔，3次/d，低剂量组5 mg/次，高剂量组为10 mg/次。比较各组患者肾功能指标、氧化应激指标、炎性指标、核因子-E2相关因子2(nuclear factor erythtoid 2 related factor 2，Nrf2)/抗氧化响应元件(antioxidant response element，ARE)信号通路基因mRNA相对表达水平及造影剂诱导的急性肾损伤发生率。结果 各组造影剂诱导的急性肾损伤发生率比较，对照组明显高于尼可地尔低剂量组和尼可地尔高剂量组，差异有统计学意义(P < 0.05)；与对照组相比，术后尼可地尔低剂量组和尼可地尔高剂量组血清肌酐、尿肾损伤分子1、丙二醛、C反应蛋白及白细胞介素6水平明显降低，而估算肾小球滤过率、超氧化物歧化酶、Nrf2、ARE和血红素加氧酶1 mRNA相对表达水平明显升高，差异有统计学意义(P < 0.05)；各组患者主要不良反应事件发生率的比较，差异无统计学意义(P>0.05)。结论 尼可地尔可能对老年AMI患者PCI术后造影剂诱导的急性肾损伤具有保护作用，可能与尼可地尔调节Nrf2/ARE信号通路，发挥抗氧化应激及抗炎作用有关。Abstract: Objective To explore the protection effect of nicorandil against acute kidney injury induced by contrast agent in elderly patients with acute myocardial infarction(AMI), following percutaneous coronary intervention(PCI).Methods A total of 141 elderly patients with AMI undergoing PCI in the hospital were enrolled between September 2019 and October 2021. They were randomly divided into three groups: the control group, low-dose and high-dose nicorandil groups, with 47 patients in each group. The control group was given the routine treatment regimen(aspirin+clopidogrel+ hydration therapy). On this basis, low-dose and high-dose nicorandil groups were given nicorandil(3 times/d; low-dose group: 5 mg/once, high-dose group: 10 mg/once) during the period from 30 min before surgery to 3 d after surgery. The renal function indexes, oxidative stress indexes, inflammatory indexes, mRNA related expression levels of nuclear factor erythtoid 2 related factor 2(Nrf2)/antioxidant response element(ARE) signaling pathway related genes and incidence of contrast-induced AKI were compared among all groups.Results There was significant difference in incidence of contrast-induced AKI among all groups, and the incidence of contrast-induced AKI in the control group was significantly higher than that in low-dose and high-dose nicorandil groups(P < 0.05). Compared with control group, levels of serum creatinine, urinary kidney injury molecule 1, malondialdehyde, C-reactive protein and interleukin 6 were significantly decreased, while levels of estimated glomerular filtration rate and superoxide dismutase, and mRNA related expression levels of Nrf2, ARE and heme oxygenase 1 were significantly increased in low-dose and high-dose nicorandil groups after surgery(P < 0.05). There was no significant difference in incidence of main adverse reactions among all groups(P>0.05).Conclusion Nicorandil may have a protective effect against contrast-induced AKI in elderly AMI patients after PCI, which may be related to that nicorandil can regulate Nrf2/ARE signaling pathways and play the roles of anti-oxidative stress and anti-inflammation.
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Key words:
- nicorandil /
- acute myocardial infarction /
- elderly patient /
- contrast agent /
- acute kidney injury
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表 1 3组患者一般资料的比较
X±S 项目 对照组(47例) 尼可地尔低剂量组(47例) 尼可地尔高剂量组(47例) F/χ2 P 年龄/岁 67.69±6.82 69.13±7.75 68.51±7.16 0.466 0.628 性别/例 0.174 0.917 男 28 27 26 女 19 20 21 体重指数/(kg/m2) 26.59±4.28 27.35±4.64 27.86±5.02 0.885 0.415 高血压/例(%) 35(74.47) 30(63.83) 31(65.96) 1.371 0.504 糖尿病/例(%) 9(19.15) 12(25.53) 10(21.28) 0.579 0.749 总胆固醇/(mmol/L) 4.75±1.16 4.87±1.25 4.69±1.12 0.285 0.753 甘油三酯/(mmol/L) 1.86±0.56 1.93±0.61 1.97±0.65 0.394 0.675 低密度脂蛋白胆固醇/(mmol/L) 2.93±0.84 2.81±0.78 2.86±0.81 0.260 0.771 高密度脂蛋白胆固醇/(mmol/L) 1.13±0.36 1.03±0.30 1.07±0.32 1.109 0.333 造影剂用量/mL 241.69±45.11 248.56±48.37 243.61±46.28 0.272 0.762 水化用量/mL 867.23±146.29 859.75±143.36 847.55±142.40 0.224 0.800 术前用药情况/例(%) β受体阻滞剂 37(78.72) 38(80.85) 34(72.34) 1.051 0.591 抗凝剂 28(59.57) 28(59.57) 30(63.83) 0.238 0.888 ACEI/ARB类药物 36(76.60) 35(74.47) 35(74.47) 0.076 0.963 利尿剂 24(51.06) 27(57.45) 25(53.19) 0.400 0.819 他汀类药物 45(95.74) 47(100.00) 47(100.00) 4.058 0.132 注：ACEI为血管紧张素转换酶抑制剂，ARB为血管紧张素受体拮抗剂。 
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表 2 各组患者肾功能情况的比较
X±S 项目 对照组(47例) 尼可地尔低剂量组(47例) 尼可地尔高剂量组(47例) F或χ2 P 造影剂诱导的急性肾损伤/例(%) 8(17.02) 3(6.38) 1(2.13) 7.019 0.030 SCr/(μmol/L) 术前 121.63±11.42 122.25±11.14 122.84±11.86 F时间=23.115 < 0.001 术后1 d 132.45±13.46 128.51±12.85 125.23±12.211) F组间=5.732 0.003 术后2 d 139.57±14.45 133.20±13.571) 129.51±13.161) F交互=1.953 0.071 术后3 d 125.73±12.61 124.62±12.95 124.16±12.74 eGFR/[mL/(min·1.73 m2)] 术前 51.21±6.52 50.13±5.86 50.43±6.13 F时间=63.413 < 0.001 术后1 d 44.26±5.14 47.59±5.381) 48.65±5.711) F组间=13.640 < 0.001 术后2 d 38.96±4.21 42.16±4.871) 45.63±5.321)2) F交互=4.329 < 0.001 术后3 d 48.55±5.42 49.86±5.75 50.19±5.90 尿KIM-1/(μg/L) 术前 63.75±7.18 65.71±7.94 64.74±7.56 F时间=161.415 < 0.001 术后1 d 81.82±9.35 78.37±8.631) 72.41±7.751)2) F组间=36.075 < 0.001 术后2 d 92.37±10.58 84.32±9.571) 74.85±8.031)2) F交互=10.966 < 0.001 术后3 d 68.36±8.11 67.59±7.89 65.34±7.24 与对照组比较，1)P < 0.05；与尼可地尔低剂量组比较，2)P < 0.05。
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表 3 各组氧化应激和炎性指标的比较
X±S 项目 对照组(47例) 尼可地尔低剂量组(47例) 尼可地尔高剂量组(47例) F P MDA/(μmol/L) 术前 2.12±0.65 2.01±0.58 2.07±0.62 0.374 0.689 术后3 d 2.95±0.84 2.74±0.77 2.49±0.731) 4.083 0.019 SOD/(IU/mL) 术前 72.65±8.54 71.29±8.06 70.78±7.84 0.661 0.518 术后3 d 59.26±6.41 63.75±6.911) 68.59±7.271)2) 21.667 < 0.001 CRP/(mg/L) 术前 4.82±1.34 4.95±1.48 4.86±1.37 0.107 0.899 术后3 d 18.95±5.21 16.49±4.671) 13.27±3.161)2) 19.411 < 0.001 IL-6/(ng/L) 术前 127.65±15.68 125.43±13.75 128.54±16.23 0.518 0.597 术后3 d 152.49±20.14 143.58±18.641) 131.46±17.851)2) 14.660 < 0.001 与对照组比较，1)P < 0.05；与尼可地尔低剂量组比较，2)P < 0.05。
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表 4 各组Nrf2/ARE信号通路基因mRNA相对表达水平比较
X±S 项目 对照组(47例) 尼可地尔低剂量组(47例) 尼可地尔高剂量组(47例) F P Nrf2 术前 1.13±0.20 1.08±0.17 1.15±0.22 1.563 0.213 术后3 d 0.64±0.17 0.71±0.141) 0.88±0.181)2) 26.550 < 0.001 ARE 术前 1.54±0.23 1.57±0.25 1.48±0.19 1.954 0.146 术后3 d 0.87±0.18 1.04±0.20 1.21±0.24 31.345 < 0.001 ho-1 术前 1.19±0.25 1.15±0.22 1.21±0.17 1.311 0.273 术后3 d 0.74±0.14 0.83±0.171) 0.98±0.151)2) 29.193 < 0.001 与对照组比较，1)P < 0.05；与尼可地尔低剂量组比较，2)P < 0.05。
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