Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg⁻¹· d⁻¹, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1–100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.

肾小管近端损伤是糖尿病性肾脏疾病（DKD）的关键过程。我们以前的研究表明，前列腺素E1（PGE1）可以减少DKD大鼠肾小管细胞的凋亡。但其潜在机制仍不清楚。在这项研究中，我们调查了PGE1对DKD大鼠和高葡萄糖（HG，30 mM）处理的HK-2近端肾小管细胞的保护作用。建立非全切除的链脲佐菌素诱导的糖尿病大鼠四周后，给DKD大鼠施用PGE1（10μg·kg ^-1 ·d ^-1，iv。）连续10天。我们显示，PGE1给药不会改变血糖水平，但可以减轻DKD大鼠的糖尿病性肾脏损伤，这可通过蛋白尿和肾小管凋亡的明显减少来证明。在体外实验中，PGE1（0.1–100 µM）显着增强了HG降低的HK-2细胞的活力。在经过HG处理的HK-2细胞中，PGE1（10 µM）显着抑制了c-Jun N末端激酶（JNK）和线粒体凋亡相关蛋白的表达，例如Bim，Bax，caspase-3和裂解的caspase-3。在PGE1处理的DKD大鼠的肾脏中也观察到了类似的变化。通过使用两种药理学工具-JNK激活茴香霉素（AM）和JNK抑制剂SP600125，我们发现PGE1阻断了HG触发HK-2细胞中JNK / Bim途径的激活。JNK是Bim的上游监管机构。综上所述，