Ni Jingwei, Zhang Wenli, Zhu Zhengbin, Zhu Jinzhou, Du Run, Jing Yajun, Lu Lin, Zhang Ruiyan
Department of Cardiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ther Apher Dial. 2014 Dec;18(6):637-42. doi: 10.1111/1744-9987.12185. Epub 2014 Sep 26.
Uremic toxins such as p-cresyl sulfate (PCS) are associated with increased mortality for chronic kidney disease (CKD) patients, but in vivo PCS toxicity studies are limited due to the lack of a standard animal model. To establish such a model, we measured the pharmacokinetics of PCS in mice with variable renal function. Male Balb/c mice subjected to 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery (controls) were given PCS (po, 50 mg/kg). Blood samples were collected over time and plasma PCS concentrations were measured. Over 4 h, PCS was significantly higher in the plasma of CRF mice (63.28 ± 2.76 mg/L), compared to UNX mice (3.11 ± 0.64 mg/L) and controls (0.39 ± 0.12 mg/L). The PCS half-life was greatest in CRF mice (12.07 ± 0.12 h), compared to 0.79 ± 0.04 h in UNX mice and 0.48 ± 0.02 h in control mice. However, the potential presence of additional uremic toxins along with PCS in CRF mice and rapid PCS clearance in control mice suggest that the UNX mouse would be a better PCS model to study toxicity.
硫酸对甲酚（PCS）等尿毒症毒素与慢性肾脏病（CKD）患者死亡率增加相关，但由于缺乏标准动物模型，PCS的体内毒性研究有限。为建立这样一个模型，我们测定了肾功能各异的小鼠体内PCS的药代动力学。对雄性Balb/c小鼠进行5/6肾切除术（CRF）、单侧肾切除术（UNX）或不进行手术（对照组），然后给予PCS（口服，50 mg/kg）。随时间采集血样并测定血浆PCS浓度。在4小时内，CRF小鼠血浆中的PCS（63.28±2.76 mg/L）显著高于UNX小鼠（3.11±0.64 mg/L）和对照组（0.39±0.12 mg/L）。CRF小鼠的PCS半衰期最长（12.07±0.12小时），而UNX小鼠为0.79±0.04小时，对照小鼠为0.48±0.02小时。然而，CRF小鼠中可能存在除PCS之外的其他尿毒症毒素，以及对照小鼠中PCS的快速清除，这表明UNX小鼠将是研究毒性的更好的PCS模型。
