Laboratory for Medical Research, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
Exp Gerontol. 2013 Feb;48(2):298-303. doi: 10.1016/j.exger.2012.11.006. Epub 2012 Nov 23.
The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n=6) or not (n=6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.
这项研究的目的是评估 N-乙酰半胱氨酸（NAC）对老年大鼠肾脏功能以及钠和水转运蛋白的影响。将正常的 8 月龄雄性 Wistar 大鼠分为（n=6）治疗组或未治疗组（n=6），用 NAC（饮用水中 600mg/L）治疗 16 个月。在随访期末，我们测定了菊粉清除率、血清硫代巴比妥酸反应物（TBARS）、血清胆固醇和尿磷酸盐排泄率。此外，我们进行了 p53 和 ED-1 阳性细胞（巨噬细胞/单核细胞）的免疫组织化学染色，以及肾组织 NKCC2、水通道蛋白 2（AQP2）、尿素转运蛋白 A1（UT-A1）和 Klotho 蛋白的 Western blot。在基线时，两组大鼠的肌酐清除率、蛋白尿、胆固醇和 TBARS 相似。在随访期末，与未治疗组相比，NAC 治疗组的大鼠具有更高的菊粉清除率和降低的蛋白尿，同时血清胆固醇、血清 TBARS 和尿磷酸盐排泄率更低。此外，NAC 治疗组大鼠 NKCC2、AQP2 和 UT-A1 的表达上调，Klotho 蛋白表达升高，p53 表达降低，ED-1 阳性细胞较少。综上所述，我们认为 NAC 的这些有益作用（菊粉清除率和 NKCC2、AQP2 和 UT-A1 的表达显著改善）归因于其降低氧化应激、抑制 p53 表达、最小化肾脏炎症和刺激 Klotho 表达的能力。
