Pawlak Krystyna, Pawlak Dariusz, Mysliwiec Michal
Department of Nephrology and Transplantation, Medical University, 14 Zurawia Street, 15-540 Bialystok, Poland.
Cytokine. 2004 Dec 21;28(6):197-204. doi: 10.1016/j.cyto.2004.07.007.
HBV and HCV infections are associated with the increased production of reactive oxygen species (ROS) within the liver that are responsible for the oxidation of intracellular molecules and activation transcription factors. The aim of the present study was to establish whether the presence of hepatitis could be implicated in the elevation of oxidative stress (SOX) and plasma proinflammatory and chemoattractant cytokine levels in uraemic patients. The markers of SOX-autoantibodies to oxidized LDL (OxLDL-Ab); total peroxides; and the major antioxidant enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD); as well as tumor necrosis factor-alpha (TNF-alpha); regulated upon activation, normal T cell expressed and secreted (RANTES); and macrophage inflammatory protein-1alpha (MIP-1alpha) and beta (MIP-1beta) levels were measured in the plasma of uraemic patients with hepatitis in comparison to subjects without hepatitis and to healthy volunteers. The values of total peroxide, Cu/Zn SOD, TNF-alpha, and MIP-1beta, were significantly elevated in uraemic patients when compared to the controls, whereas RANTES were decreased. MIP-1alpha and OxLDL-Ab were similar in the two groups. Cu/Zn SOD, MIP-1beta and RANTES concentrations were significantly higher in the hepatitis-positive relative to the hepatitis-negative group. Both MIP-1beta and RANTES were directly associated with Cu/Zn SOD levels and the presence of hepatitis. Multiple stepwise regression analysis has shown that the duration of dialysis, followed by the presence of hepatitis, independently and significantly predicted increased Cu/Zn SOD levels, whereas elevated Cu/Zn SOD as an independent variable was significantly associated with both increased both MIP-1beta and RANTES in uraemic patients. These results suggest that the presence of viral hepatitis status and liver injury are novel determinants of increased oxidative stress, as well as of increased MIP-1beta and RANTES levels in uraemic patients.
乙肝病毒(HBV)和丙肝病毒(HCV)感染与肝脏内活性氧(ROS)生成增加有关,ROS会导致细胞内分子氧化并激活转录因子。本研究的目的是确定肝炎的存在是否与尿毒症患者氧化应激(SOX)升高以及血浆促炎和趋化因子细胞因子水平有关。检测了SOX的标志物——氧化型低密度脂蛋白自身抗体(OxLDL-Ab)、总过氧化物,以及主要抗氧化酶铜/锌超氧化物歧化酶(Cu/Zn SOD),同时检测了肿瘤坏死因子-α(TNF-α)、活化调节正常T细胞表达和分泌因子(RANTES),以及巨噬细胞炎性蛋白-1α(MIP-1α)和β(MIP-1β)在患有肝炎的尿毒症患者血浆中的水平,并与无肝炎的患者及健康志愿者进行比较。与对照组相比,尿毒症患者的总过氧化物、Cu/Zn SOD、TNF-α和MIP-1β水平显著升高,而RANTES水平降低。两组的MIP-1α和OxLDL-Ab水平相似。肝炎阳性组的Cu/Zn SOD、MIP-1β和RANTES浓度显著高于肝炎阴性组。MIP-1β和RANTES均与Cu/Zn SOD水平及肝炎的存在直接相关。多元逐步回归分析表明,透析时间,其次是肝炎的存在,独立且显著地预测了Cu/Zn SOD水平的升高,而升高的Cu/Zn SOD作为自变量与尿毒症患者MIP-1β和RANTES的升高均显著相关。这些结果表明,病毒性肝炎状态和肝损伤的存在是尿毒症患者氧化应激增加以及MIP-1β和RANTES水平升高的新决定因素。