Division of Urology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Neurourol Urodyn. 2011 Mar;30(3):472-9. doi: 10.1002/nau.20855. Epub 2011 Feb 8.
Oxidative stress and endoplasmic reticulum (ER) stress may induce renal apoptosis and contribute to the pathogenesis of the kidney with unilateral ureteral obstruction (UUO).
We induced UUO the female Wistar rats by ligation of the left ureter at the ureteropelvic junction. The UUO kidney was performed from 4 hr to 7 days course. At the indicated time, we measured the arterial blood pressure and renal blood flow in each rat, renal ROS measurement in vivo by a chemiluminescence analyzer. We performed immunohistochemistry of monocyte/macrophage (ED-1) stain for leukocyte infiltration, 4-hydroxynoneal (4-HNE) stain for ROS products, and apoptosis by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and Western blot to analyze ER stress-associated and apoptosis-related proteins expression in the UUO kidney.
We found that UUO decreased renal blood flow and increased renal vascular resistance and renal ROS. UUO decreased renal manganese superoxide dismutase (MnSOD) and catalase protein expression in a time-dependent manner. Increased 4-HNE stain in the renal tubules and ED-1 stain in the renal tubulointerstitial compartment occurred after 4 hr of UUO in the kidney. UUO significantly enhanced ER stress markers like ER stress-response protein 25 and glucose-regulated protein 78 and ER-associated apoptosis proteins, c-JUN NH(2) -terminal kinase, and caspase 12, in the kidney. Subsequently, UUO enhanced renal pro-apoptotic Bax and caspase 3 expression and decreased anti-apoptotic Bcl-2 expression, leading to renal tubular apoptosis.
Our data suggest that renal tubular apoptosis induced by oxidative stress and ER stress occurred in the UUO kidney.
氧化应激和内质网（ER）应激可能诱导肾脏细胞凋亡，并有助于单侧输尿管梗阻（UUO）肾脏的发病机制。
我们通过结扎左输尿管肾盂交界处，诱导雌性 Wistar 大鼠发生 UUO。UUO 肾脏模型的造模时间为 4 小时至 7 天。在指定时间，我们测量了每只大鼠的动脉血压和肾血流量，通过化学发光分析仪在体内测量肾脏 ROS 水平。我们进行了单核细胞/巨噬细胞（ED-1）染色的免疫组织化学，以分析白细胞浸润；4-羟基壬烯醛（4-HNE）染色以分析 ROS 产物；末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）和 Western blot 分析 UUO 肾脏中 ER 应激相关和凋亡相关蛋白的表达。
我们发现 UUO 降低了肾血流量，增加了肾血管阻力和肾 ROS。UUO 呈时间依赖性降低肾脏锰超氧化物歧化酶（MnSOD）和过氧化氢酶蛋白的表达。在 UUO 发生后 4 小时，肾脏肾小管中 4-HNE 染色增加，肾小管间质腔中 ED-1 染色增加。UUO 显著增强了 ER 应激标志物，如 ER 应激反应蛋白 25 和葡萄糖调节蛋白 78，以及 ER 相关凋亡蛋白 c-JUN NH2-末端激酶和半胱天冬酶 12 在肾脏中的表达。随后，UUO 增强了肾脏促凋亡 Bax 和半胱天冬酶 3 的表达，降低了抗凋亡 Bcl-2 的表达，导致肾小管细胞凋亡。
我们的数据表明，氧化应激和 ER 应激诱导的肾小管细胞凋亡发生在 UUO 肾脏中。
