抗坏血酸透析液改善维持性血液透析患者氧化应激的初步研究

Preliminary application of ascorbate-rich dialysate on ameliorating oxidative stress in maintenance hemodialysis patients

目的观察应用抗坏血酸透析液对维持性血液透析(MHD)患者氧化应激的影响,并与经静脉途径补充抗坏血酸进行比较。方法(1)单次透析:8例MHD患者进行3次透析,每次为一组,分别为①对照组(con-trol);②静脉抗坏血酸(iv-AA)组;③透析液抗坏血酸(D-AA)组:使用含抗坏血酸2g/L的浓缩酸性透析液(A液)。每小时取血标本测定血浆总抗坏血酸(TAA)、脱氢型抗坏血酸/总抗坏血酸(DHAA/TAA)、维生素E(VitE)、血浆与红细胞丙二醛(MDA)。(2)抗坏血酸透析4周:23名MHD患者随机分为对照组(n=12)和试验组(n=11,使用含抗坏血酸0.8g/L的浓缩A液)。检测两组对象试验前、4周后的上述氧化应激指标和氧化型低密度脂蛋白(oxLDL)、高级蛋白质氧化产物(AOPP)及血清C反应蛋白(CRP),血清铁蛋白(SF)、血液学指标。结果(1)透析过程中对照组血浆TAA水平逐渐降低,血浆MDA值升高[透析后(8.47±3.45)μmol/Lvs透析前(5.12±1.15)μmol/L,P<0.05]。静脉注射抗坏血酸后血浆TAA呈现浓度峰值而DHAA/TAA相应降低,随即TAA下降,至透析结束时回复至透前水平。D-AA组中血浆TAA水平基本保持稳定,近透析结束时血浆VitE略升高[透析后(26.7±2.8)μmol/Lvs透析前(22.4±0.9)μmol/L,P<0.001]。(2)观察4周后试验组的血浆TAA水平增高[试验后(83.8±56.5)μmol/Lvs试验前(32.6±25.2)μmol/L,P<0.05]。血浆oxLDL在试验组降低[试验前(27.4±13.3)mg/dLvs试验后(16.8±9.5)mg/dL,P<0.05]。结论血透过程中大量抗坏血酸丢失,患者的氧化应激程度加重。静脉补充抗坏血酸或应用抗坏血酸透析液均能减少其损失,削弱氧化应激,但后者的抗氧化作用更趋于平稳缓和。

Purpose To observe the effects of ascorbate （vitamin C, Vit C） dialysate on oxidative stress in maintenance hemodialysis （MHD） patients, particularly in comparison with those of intravenous ascorbate supplementation. Methods （1） Single dialysis session： 8 MHD patients performed three successive dialysis sessions, and each course was taken as a group. They were respectively： ①control group; ②iv-AA group; ③D-AA group（using ascorbate-containing acid dialysate of 2 g/L）. Blood samples were drawn every hour during each course for determining plasma total ascorbic acid （TAA）, ratio of dehydroascorbic acid（DHAA） to TAA（DHAA/TAA）, vitamin E（Vit E）, malondialdehyde（MDA） in both plasma and erythrocytes. （2） 4-week application of ascorbate-rich dialysate： Twenty-four MHD patients were randomly divided into control group（n = 12） and experimental group （n= 11, with use of acid dialysate containing ascorbic acid 0.8 g/L）. The above-mentioned oxidative stress markers, oxidized low density lipoprotein （oxLDL）, advanced oxidation protein products （AOPP）, serum C-reactive protein（CRP）, serum ferritin（SF） and hematological indices were examined before and after the 4-week period. Results （1） Plasma TAA gradually decreased during the course of dialysis in control group, meanwhile MDA showed a moderate and significant increase [postdialysis （8.47 ± 3.45） /zmol/L vs pre-dialysis （5.12 ± 1.15）μmol/L,P〈0.05]. A TAA concentration peak protruded in the curve right after injection of ascorbic acid, accompanied by dramatic reduction of DHAA/TAA. However,a precipitous fall of TAA soon followed and ultimately reverted to the similar level at the beginning of dialysis. Plasma TAA concentration remained table and VitE level slightly elevated in D-AA groupl-post-dialysis （26.7 ± 2.8） μmol/L vs pre-dialysis （22.4 ± 0.9） μmol/ L,P〈0. 001]. （2） Plasma TAA augmented in experimental group at the end of the 4-week investigation[at the end （83.8 ± 56.5） μmol/L vs at the start （32.6 ±25.2） μol/L, P〈0.05], and plasma oxLDL value became lower in the experimental group. Conclusions Plenty of plasma ascorbic acid losses in hemodialysis while oxidative stress is exacerbated. Ascorbic acid supplementation via either intravenous injection or extracorporeal circuit will alleviate loss of this antioxidant and help attenuate oxidative stress, but internal exquisite change will probably be avoided only by the latter means.