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目的探讨阿托伐他汀联合普罗布考治疗对经皮冠状动脉介入治疗(PCI)术后造影剂肾病(CIN)的预防作用、安全性及可能机制。方法入选2013年2月至2015年6月于天津市胸科医院心内科行择期PCI术的冠状动脉性心脏病(冠心病)患者共330例,按随机数字表法随机分为3组:常规剂量阿托伐他汀组(A组,n=110)、强化剂量阿托伐他汀组(B组,n=110)、常规剂量阿托伐他汀联合普罗布考组(C组,n=110)。A组:术前1d开始给予阿托伐他汀20mg,1次/晚;B组:术前1d开始给予阿托伐他汀40mg,1次/晚;C组:术前1d开始给予阿托伐他汀20mg,1次/晚和普罗布考250mg,3次/d。3组患者均于PCI术后4d开始仅给予阿托伐他汀20mg,1次/晚。收集3组患者的基本资料、造影剂用量,并记录PCI术前及术后72h的血清肌酐、血尿素氮、估算的肾小球滤过率(eGFR)、高敏C反应蛋白(hsCRP)、丙二醛、丙氨酸氨基转移酶(ALT)水平的变化。记录3组患者CIN发生情况、住院期间阿托伐他汀及普罗布考的不良反应。结果 3组患者术前基线资料差异无统计学意义(P>0.05)。B组和C组CIN发生率低于A组(1.8%,2.7%比10.0%,均P<0.05);B组与C组CIN发生率差异无统计学意义(P>0.05)。PCI术后72h,A组患者的肌酐、尿素氮水平较术前升高,eGFR水平较术前下降(均P<0.05);B组、C组患者的肌酐、尿素氮水平低于A组[(80.99±16.65),(81.79±17.96)比(93.30±20.97)μmol/L;(5.78±0.92),(6.05±1.29)比(6.18±1.08)mmol/L],eGFR水平高于A组[(78.80±26.04),(75.42±20.81)比(69.39±22.81)mL/(min·1.73m~2),均P<0.05]。PCI术后,3组患者的hsCRP、丙二醛水平较术前升高(均P<0.05);B组和C组患者的hsCRP、丙二醛水平低于A组。多因素Logistic回归分析显示强化他汀(OR=0.093,95%CI0.016~0.533,P=0.008)及他汀联合普罗布考(OR=0.252,95%CI 0.068~0.931,P=0.039)是CIN的保护因素;住院期间,3组患者均未出现明显肝损害、肌无力等不良事件。结论强化剂量阿托伐他汀及常规剂量阿托伐他汀联合普罗布考均能降低CIN的发生率,并且有良好的安全性,其机制可能与抑制炎症、氧化应激反应有关。
Objective To investigate the preventive effect, safety and possible mechanism of atorvastatin combined with probucol on CIN after percutaneous coronary intervention (PCI). Methods A total of 330 patients with coronary heart disease (CHD) undergoing elective PCI during Cardiology of Tianjin Chest Hospital from February 2013 to June 2015 were randomly divided into 3 groups according to random number table: routine Atorvastatin group (group A, n = 110), atorvastatin group (group B, n = 110), normal dose of atorvastatin combined with probucol group (n = 110) . Group A: Atorvastatin 20 mg, once / night was given on the first day before operation; Group B: Atorvastatin 40 mg, once / night was given on the first day before operation; Group C: Atorvastatin 20mg, once / night and probucol 250mg, 3 times / d. All patients in the three groups received atorvastatin 20 mg once daily for 4 days after PCI. The basic data of 3 groups of patients were collected, the dosage of contrast medium was recorded, and serum creatinine, blood urea nitrogen, estimated glomerular filtration rate (eGFR), high sensitivity C-reactive protein (hsCRP) Dialdehyde, alanine aminotransferase (ALT) levels. The incidence of CIN, adverse reactions of atorvastatin and probucol during the hospital stay were recorded. Results There was no significant difference in preoperative baseline data between the three groups (P> 0.05). The incidence of CIN in group B and C was lower than that in group A (1.8%, 2.7% vs 10.0%, both P <0.05). There was no significant difference in CIN between group B and C (P> 0.05). At 72h after PCI, creatinine and urea nitrogen levels in group A were significantly higher than those before surgery and eGFR levels were lower than those before surgery (all P <0.05); creatinine and urea nitrogen levels in group B and group C were lower than those in group A [ (80.99 ± 16.65), (81.79 ± 17.96) vs (93.30 ± 20.97) μmol / L, (5.78 ± 0.92) vs (6.05 ± 1.29) vs (6.18 ± 1.08) mmol / L] (78.80 ± 26.04), (75.42 ± 20.81) vs (69.39 ± 22.81) mL / (min · 1.73m ~ 2), all P <0.05]. After PCI, the levels of hsCRP and MDA in all three groups were significantly higher than those before surgery (both P <0.05). The levels of hsCRP and MDA in group B and C were lower than those in group A. Multivariate logistic regression analysis showed that statin (OR = 0.093, 95% CI0.016-0.533, P = 0.008) and statin combined with probucol (OR = 0.252, 95% CI 0.068-0.931, P = 0.039) Protection factors; During hospitalization, no significant adverse events such as liver damage and muscle weakness were found in the three groups of patients. Conclusions Fortified doses of atorvastatin and routine dose of atorvastatin combined with probucol can reduce the incidence of CIN, and have good safety, the mechanism may be related to inhibition of inflammation and oxidative stress.