目的·探究淫羊藿苷在急性肾损伤（acute kidney disease，AKI）向慢性肾脏病（chronic kidney disease，CKD）转化中的作用并探讨其可能的机制。方法·C57BL/6小鼠腹腔注射马兜铃酸2周，制作AKI向CKD转化模型，并于造模前1周或马兜铃酸注射2周结束时持续灌胃给予淫羊藿苷5周或2周。监测小鼠肾功能和肾脏病理损伤，并用透射电子显微镜观察肾小管上皮细胞线粒体结构，采用荧光定量PCR（qPCR）及免疫组织化学染色法检测脂肪酸氧化代谢通路、纤维化及炎症指标等。采用Transwell细胞小室共培养大鼠肾脏成纤维细胞株和大鼠肾小管上皮细胞株，模拟2种细胞之间的相互作用。先提前1 h在肾小管上皮细胞培养液中加入淫羊藿苷，再加入马兜铃酸干预24 h；去除药物干预后，将肾小管上皮细胞与成纤维细胞共培养24 h。qPCR或Western blotting检测肾脏上皮细胞过氧化物酶体增殖物激活受体α（peroxisome proliferator activated receptor α，Ppara）、促纤维化因子、炎症因子、活化胱天蛋白酶（cleaved caspase-3），以及肾脏成纤维细胞细胞外基质相关基因mRNA或蛋白表达的变化。用Ppara-siRNA转染肾小管上皮细胞，观察淫羊藿苷提前于马兜铃酸干预后PPARα下游线粒体脂肪酸氧化代谢相关指标以及cleaved caspase-3的表达变化。结果·马兜铃酸注射2周结束时和注射结束后2周（造模4周），仅注射马兜铃酸的小鼠血清肌酐及尿素氮水平较对照组均显著升高，肾脏炎症细胞大量浸润，肾小管损伤严重；而提前给予淫羊藿苷干预的小鼠较马兜铃酸组肾功能明显改善，肾脏病理损伤减轻。造模4周时马兜铃酸组肾小管上皮细胞线粒体结构损伤严重，脂肪酸氧化代谢通路相关基因mRNA水平较对照组显著降低，伴巨噬细胞浸润及肾纤维化，提前给予淫羊藿苷干预后上述损伤或指标均明显缓解。在马兜铃酸注射2周结束时给予淫羊藿苷的小鼠血清肌酐和尿素氮水平、肾脏病理损伤、纤维化指标均与马兜铃酸组无明显差异。体外实验中，马兜铃酸可抑制肾小管上皮细胞Ppara mRNA表达，促进cleaved caspase-3、炎症因子及促纤维化因子表达升高，并上调共培养的肾脏成纤维细胞细胞外基质相关基因的表达，而淫羊藿苷提前干预对上述变化有明显的纠正作用。用siRNA敲低肾小管上皮细胞的Ppara后，淫羊藿苷对马兜铃酸抑制脂肪酸氧化代谢及促进细胞凋亡的预防保护作用减弱。结论·淫羊藿苷能预防马兜铃酸诱导的小鼠AKI向CKD转化；它可能是通过改善肾小管上皮细胞线粒体脂肪酸氧化代谢通路（尤其是PPARα）发挥作用。

Objective ·To investigate the effect of icariin on the transition from acute kidney disease (AKI) to chronic kidney disease (CKD) in mice and the possible mechanism. Methods ·C57BL/6 mice were intraperitoneally injected with aristolochic acid for 2 weeks to mimic AKI to CKD transition. Icariin was intragastrically administered for 2 or 5 weeks at the end of 2 weeks of aristolochic acid injection or 1 week before modeling. The renal function and pathological injury of the mice were monitored. The mitochondrial structure of renal tubular epithelial cells was observed by transmission electron microscopy. The indexes related to fatty acid oxidative metabolic pathway, fibrosis, and inflammation were detected by quantitative PCR (qPCR) and immunohistochemical staining. The rat renal fibroblast cell line and the rat renal tubular epithelial cell lines were co-cultured in Transwell cell chambers to simulate the interaction between the two types of cells. The renal tubular epithelial cells were pretreated with icariin for 1 h, and then treated with aristolochic acid for 24 h. After removing the two drugs, the renal tubular epithelial cells and the fibroblasts were co-cultured for 24 h. The mRNA or protein expression levels of peroxisome proliferator-activated receptor α (Ppara), pro-fibrotic factors, inflammatory factors, activated caspase-3 (cleaved caspase-3), and extracellular matrix-associated genes in renal fibroblasts were detected by qPCR or Western blotting. The renal tubular epithelial cells were transfected with Ppara-siRNA to observe the expression changes of cleaved caspase-3 and the related indicators of mitochondrial fatty acid oxidative metabolism in the downstream of PPARα after icariin intervention prior to aristolochic acid. Results ·Compared with the control group, the serum creatinine and urea nitrogen levels of the mice injected with aristolochic acid only were significantly higher, with a large number of inflammatory cells infiltrating into the kidney and serious renal tubular injury at the end of 2 weeks of aristolochic acid injection and 2 weeks after the last injection (4 weeks). The renal function was significantly improved, and the pathological damage was attenuated in the mice pretreated with icariin. After 4 weeks of modeling, the mitochondrial structure of renal tubular epithelial cells was seriously damaged in the aristolochic acid group, and the mRNA levels of fatty acid oxidative metabolic pathway-related genes were significantly downregulated, compared to the control group, accompanied by macrophage infiltration and renal fibrosis. Icariin pretreatment attenuated these damages generated by aristolochic acid. The serum creatinine and urea nitrogen levels, renal pathological injury, and fibrotic markers of the mice treated with icariin at the end of 2 weeks of aristolochic acid injection showed no difference from the aristolochic acid group. In the in vitro experiments, aristolochic acid treatment suppressed Ppara mRNA expression and elevated cleaved caspase-3, inflammatory factors, and pro-fibrotic factors in renal tubular epithelial cells. It also upregulated the expression of extracellular matrix-related genes in co-cultured renal fibroblasts. In contrast, icariin pretreatment abrogated the changes caused by aristolochic acid. The knockdown of Ppara by siRNA in renal tubular epithelial cells removed the preventive effects of icariin on aristolochic acid inhibiting fatty acid oxidative metabolism and promoting cell apoptosis. Conclusion ·Icariin prevents AKI to CKD transition induced by aristolochic acid in mice. It may play its protective role by improving the mitochondrial fatty acid oxidative metabolic pathway, especially through PPARα, in renal tubular epithelial cells.