Objective: To investigate the preventive effect, possible mechanism and safety of probucol on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods: A total of 641 patients with coronary heart disease were consecutively enrolled from Department of Cardiology, in Tianjin Chest Hospital, Tianjin TEDA International Cardiovascular Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital. They were randomly divided into probucol group (n=321) and control group (n=320). The probucol group was given oral probucol 500 mg twice daily for day 0 to day 3 after PCI; the control group was given only conventional therapy. All patients were given intravenous drip 0.9% sodium chloride solution before 12 to 24 hours of operation. The levels of serum creatinine (Scr), blood urea nitrogen (BUN), evaluate glomerular filtration rate (eGFR), cystatin C (Cys-C), and high-sensitivity C-reactive protein (hs-CRP), neutrophil gelatinase associated lipocalin (NGAL), superoxide dismutase (SOD) and glutathione (GSH) were measured before and 72 h after the PCI operation in both groups. The incidence rates of CIN, the adverse events during hospitalization and postoperative 14-day follow-up were recorded in two groups. Results: There was no statistically significantly difference in the levels of Scr, BUN, eGFR, Cys-C, hs-CRP, NGAL, SOD and GSH between the two groups before PCI (P>0.05). The levels of serum Scr, BUN, Cys-C, hs-CRP, NGAL, SOD and GSH after operation in the two groups were higher than those before the operation (P<0.05). The levels of hs-CRP and NGAL in the probucol group were lower than those in the control group [(10±4) vs (11±4)mg/L, (25±8)vs (34±7)U/ml, P<0.05]. The levels of eGFR, SOD and GSH in probucol group were higher than those in control group [(80±27) vs (72±26) ml·min(-1)·1.73 m(-2,) (67±9) vs (58±8)U/ml, (4.6±0.9) vs (3.9±0.8)U/ml, P<0.05]. The incidence of CIN was 4.0% in the probucol group and 10.9% in the control group, and the difference was statistically significant (P<0.05, χ(2)=-3.31). Multivariate Logistic regression analysis showed that probucol was an independent protective factor for CIN (OR=0.334, 95%CI 0.172-0.648, P=0.001). There were no adverse events such as myasthenia gravis, abnormal liver function and cardiovascular events during the hospitalization and 14-day follow-up. Conclusions: Probucol can reduce the incidence of contrast-induced nephropathy after PCI. The protection mechanism is related with its anti-inflammatory and anti-oxidative stress effects, and it has good safety.
目的： 探讨普罗布考对冠心病患者介入治疗(PCI)术后对比剂肾病(CIN)的预防作用、可能的作用机制及安全性。 方法： 连续入选2015年11月至2016年11月于天津市胸科医院、天津市泰达国际心血管病医院、天津市第一中心医院、天津市第四中心医院四所医院心内科行择期PCI术的冠心病患者共641例。按照随机数字表法分为两组：普罗布考组(n＝321)及对照组(n＝320)。其中普罗布考组于PCI术前1 d至术后3 d，每日给予患者口服普罗布考500 mg，每天2次；对照组仅给予常规治疗。2组患者均于术前12～24 h给予静脉点滴0.9%氯化钠溶液水化。分别观察两组患者PCI术前及术后72 h的血清肌酐(Scr)、血尿素氮(BUN)、肾小球滤过率估算值(eGFR)、胱抑素C(Cys－C)、超敏C－反应蛋白(hs－CRP)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)指标的变化，并记录两组患者CIN的发生情况，住院及术后14 d随访期间有无不良反应事件发生。 结果： 两组术前血Scr、BUN、eGFR、Cys－C、hs－CRP、NGAL 、SOD、GSH水平比较，差异无统计学意义(P>0.05)。两组术后72 h血Scr、BUN、Cys－C、hs－CRP、NGAL 、SOD、GSH水平均较术前升高(P<0.05)，普罗布考组hs－CRP、NGAL水平低于对照组[(10±4)比(11±4)mg/L、(25±8)比(34±7)U/ml，P<0.05]，普罗布考组eGFR、SOD、GSH水平高于对照组[(80±27)比(72±26)ml·min(－1)·1.73 m(－2)、(67±9)比(58±8)U/ml、(4.6±0.9)比(3.9±0.8)U/ml、P<0.05]。普罗布考组CIN发生率4.0%，对照组CIN发生率为10.9%，两组比较差异有统计学意义(P<0.05，χ(2)＝－3.31)。多元Logistic回归分析结果显示，普罗布考是对比剂肾病的独立保护因素(OR＝0.334，95% CI 0.172～0.648，P＝0.001)，住院期间及术后14 d随访期间两组患者均未出现肌无力、肝功能异常、心血管事件等不良反应。 结论： 普罗布考对冠心病患者介入治疗术后对比剂肾病可能起到一定预防保护作用，其作用机制可能与普罗布考的抗炎、抗氧化应激作用有关，且具有良好的安全性。.
Keywords: Contrast media; Coronary heart disease; Nephrosis; Percutaneous coronary intervention; Prevention; Probucol.