Shi Min, Ma Liang, Zhou Li, Fu Ping
Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Molecules. 2016 Oct 18;21(10):1391. doi: 10.3390/molecules21101391.
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.
马兜铃酸肾病（AAN）是一种由含有马兜铃酸的中草药引起的进行性肾脏疾病。肾小管上皮细胞（RTECs）的过度死亡是AAN急性期的特征。急性AAN的治疗方法有限，如类固醇和血管紧张素受体阻滞剂（ARBs）/血管紧张素转换酶抑制剂（ACEIs）。有趣的是，在急性AAN中，女性患者向肾衰竭进展的速度相对比男性慢。在先前的一项研究中，发现女性激素17β-雌二醇（E2）可减轻肾脏缺血再灌注损伤。因此，本研究的目的是探讨E2在急性AAN中的潜在保护作用。与急性AAN的雄性C57BL/6小鼠相比，发现雌性小鼠血清肌酐（SCr）较低，肾损伤较轻，同时伴有RTEC凋亡。用E2治疗雄性AAN小鼠可降低SCr水平，减轻肾小管损伤和RTEC凋亡。在小鼠肾组织和人肾近端小管细胞（HK-2细胞）中，E2既能减轻AA诱导的细胞凋亡，又能下调磷酸化p53（Ser15）、p53和裂解的半胱天冬酶-3的表达。本研究强调，E2通过减少RTEC凋亡对雄性小鼠急性AAN的肾损伤具有保护作用，这可能与抑制p53信号通路有关。
