Ni Zhenmin, Hou Stephen, Barton Cyril H, Vaziri Nosratola D
Division of Nephrology and Hypertension, University of California, Irvine, Irvine, California, USA.
Kidney Int. 2004 Dec;66(6):2329-36. doi: 10.1111/j.1523-1755.2004.66032.x.
Chronic lead exposure causes hypertension and cardiovascular disease, which are associated with, and, in part, due to oxidative stress. While occurrence of oxidative stress in lead-exposed animals and cultured endothelial cells has been well-established, direct and specific evidence on the type of the reactive oxygen species (ROS) produced by lead-exposed vascular cells is lacking and was investigated.
Human coronary endothelial (EC) and vascular smooth muscle cells (VSMC) were incubated in appropriate culture media in the presence of either 1 ppm or 10 ppm lead acetate or sodium acetate (control) for 1 to 30 minutes or 60 hours. Productions of superoxide and hydrogen peroxide in the cell populations were determined by flow cytometry using hydroethidine and dihydrorhodamine, respectively. Data from a minimum of 10,000 cells were collected and analyzed using Cell Quest software. In addition, Cu Zn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and NAD(P)H oxidase (gp91phox) were measured.
Short-term lead exposure resulted in a significant rise in both superoxide and hydrogen peroxide production by both EC and VSMC. After long-term exposure, detectable superoxide levels fell to near normal level, while hydrogen peroxide production remained high. This was associated with up-regulations of gp91phox, elevation of superoxide dismutase, reduction of VSMC catalase, and no change in GPX levels. Together, these events can account for the observed decline in superoxide and the rise in hydrogen peroxide following long-term lead exposure.
Lead exposure promotes generation of superoxide and hydrogen peroxide in human EC and VSMC. This phenomenon can potentially contribute to the pathogenesis of the lead-associated hypertension and cardiovascular disease, and points to the potential benefit of lowering lead burden in the exposed populations.
长期铅暴露会导致高血压和心血管疾病，这些疾病与氧化应激相关，部分原因也在于氧化应激。虽然铅暴露动物和培养的内皮细胞中氧化应激的发生已得到充分证实，但缺乏关于铅暴露血管细胞产生的活性氧（ROS）类型的直接和具体证据，因此对此进行了研究。
将人冠状动脉内皮细胞（EC）和血管平滑肌细胞（VSMC）在含有1 ppm或10 ppm醋酸铅或醋酸钠（对照）的合适培养基中孵育1至30分钟或60小时。分别使用氢化乙锭和二氢罗丹明通过流式细胞术测定细胞群体中超氧化物和过氧化氢的产生。使用Cell Quest软件收集并分析至少10000个细胞的数据。此外，还测量了铜锌超氧化物歧化酶（SOD）、过氧化氢酶、谷胱甘肽过氧化物酶（GPX）和NAD（P）H氧化酶（gp91phox）。
短期铅暴露导致EC和VSMC中超氧化物和过氧化氢的产生均显著增加。长期暴露后，可检测到的超氧化物水平降至接近正常水平，而过氧化氢的产生仍然很高。这与gp91phox的上调、超氧化物歧化酶的升高、VSMC过氧化氢酶的降低以及GPX水平无变化有关。这些事件共同解释了长期铅暴露后观察到的超氧化物下降和过氧化氢上升的现象。
铅暴露促进人EC和VSMC中超氧化物和过氧化氢的产生。这种现象可能有助于铅相关高血压和心血管疾病的发病机制，并指出降低暴露人群铅负担的潜在益处。
