帕立骨化醇对维持性血液透析患者炎症状态及氧化应激的影响

The effects of paricalcitol on inflammatory state and oxidative stress in maintenance hemodialysis patients

目的探讨帕立骨化醇在维持性血液透析(maintenance hemodialysis,MHD)患者抗炎及抗氧化应激方面的作用。方法采取自身前后对照法。选取中国医科大学附属盛京医院第二血液净化中心MHD伴继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)患者23例。检测规律应用帕立骨化醇治疗2个月前后,测定生化指标校正后血清总钙(serum calcium after correction,cCa),血清磷(serum phosphorus,P),全段甲状旁腺激素(intact parathyroid hormone,iPTH),血清白蛋白(serum albumin,ALB));炎症指标(白细胞(white blood cell,WBC),中性粒细胞(neutrophil,NE),C-反应蛋白(c-reactive protein,CRP),白细胞介素6(Interleukin-6,IL-6),白细胞介素8(Interleukin-8,IL-8),白细胞介素10(Interleukin-10,IL-10),肿瘤坏死因子α(tumor necrosis factor-α,TNF-α);氧化应激指标(丙二醛(malondialdehyde,MDA),超氧化物歧化酶(superoxide dismutase,SOD),谷胱甘肽过氧化物酶(glutathione peroxidase,GSHPx),过氧化氢酶(catalase,CAT),硫氧还蛋白(thioredoxin,TRX)的变化。根据每月复查的生化指标的变化,调整帕立骨化醇用药剂量及剔除不符合实验标准的患者,最终完成实验21例。采用SPSS 20.0软件对所得实验结果进行统计分析。结果应用帕立骨化醇治疗2个月后:(1)炎症指标:CRP由(30.69±6.03)mg/l下降至(22.12±8.89)mg/l、IL-6由(10.44±4.52)pg/ml下降至(8.55±3.53)pg/ml、IL-8由(1637±315)pg/ml下降至(1338±221)pg/ml、TNF-α由(7.87±3.45)pg/ml下降至(6.22±2.41)pg/ml,均具有统计学意义(P值分别为0.009、0.004、0.002、0.018)。IL-10,WBC,NE变化无统计学差异。(2)氧化应激指标:SOD由(875±323)U/g升高至(1572±454)U/g,TRX由(73.0±24.6)ng/ml升高至(85.6±30.9)ng/ml,GSHPx由(75.10±12.96)U/mg升高至(84.29±20.24)U/mg,MDA由(9.31±1.93)nmol/ml下降至(7.79±2.44)nmol/ml,均具有统计学意义(P值分别为0.001,0.025,0.046,0.033)。CAT无统计学差异。结论帕立骨化醇在有效治疗SHPT的同时,对MHD患者的炎症及氧化应激状态具有改善作用。

Objective to evaluate the role of paricalcitol in anti-inflammatory and anti-oxi- dative stress in maintenance hemodialysis （MHD） patients. Methods This study employed a pre-post self-comparison design method. A total of 23 MHD patients with secondary hyper- parathyroidism （SHPT） treated in the Second Blood Purification Center, Shengjing Hospital, Chinese Medical University were enrolled in this study. After paricalcitol treatment for 2 months, the changes of biochemical, inflammatory and oxidative stress indices were evaluated in these patients. These indices included the biochemical indices of serum calcium after correc- tion （cCa）, phosphorus （P）, intact parathyroid hormone （iPTH） and albumin （ALB）; the inflam- matory indices of peripheral white blood cells （WBC） and neutrophil cells （NE）, serum C-reac- tive protein （CRP）, interleukin-6 （IL-6）, interleukin 8 （IL-8）, interleukin 10 （IL-10） and tumornecrosis factor α （TNF-α）; and the oxidative stress indices of serum malondialdehyde （MDA）; superoxide dismutase （SOD）, glutathione peroxidase （GSHPx）, catalase （CAT） and thioredoxin （TRX）. Based on the changes of biochemical indices examined monthly after the treatment, the dosage of paricalcitol was adjusted and the patients who did not meet the experimental re- quirements were excluded. A total of 21 patients finished the trial. SPSS 20.0 software was used to analyze the experimental results. Results After paricalcitol treatment for 2 months, the inflammatory indices decreased significantly, including CRP from （30.69± 6.03）mg/1 to （22.12±8.89）mg/1 （P=0.009）, IL-6 from （10.44±4.52）pg/ml to （8.55±3.53）pg/ml （P=0.004）, IL- 8 from （1637±315）pg/ml to （1338±221）pg/ml （P=0.002）, TNF-α from （7.87±3.45）pg/ml to （6.22±2.41） pg/ml （P=0.018）, but IL-10, WBC and NE had no statistical changes; oxidative stress indices increased significantly, including SOD from （875 ± 323）U/g to （1572 ± 454）U/g （P=0.001）, TRX from （73.0±24.6）ng/ml to 85.6±30.9 ng/ml （P=0.025） and GSHPx from （75.10＋ 12.96）U/mg to （84.29±20.24）U/rag （P=0.046）, but MDA decreased from 9.31± 1.93 nmol/ml to （7.79±2.44） nmol/ml （P=0.033）, and CAT had no statistical change. Conclusion Paricalcitol can effectively treat SHPT, and at the same time, can improve the inflammatory state and oxidative stress in MHD patients.