Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
Department of Urology, Memorial Sloan Kettering Cancer Center, New York, USA.
Int Urol Nephrol. 2020 Jul;52(7):1209-1218. doi: 10.1007/s11255-020-02421-1. Epub 2020 Mar 2.
Irreversible electroporation (IRE) uses microsecond-long electric pulses to kill cells through membrane permeabilization, without affecting surrounding extracellular structures. We evaluated whether IRE can be used to induce urinary obstruction for a rat model of renal scarring.
Intrasurgical IRE (2000 V/cm, 90 pulses, 100 μs) with caliper electrodes was performed in the right proximal ureter in male rats (n = 24) which were euthanized at 2, 5, or 10 days post-treatment, following contrast-enhanced magnetic resonance imaging. Complete urinary tract (bilateral kidneys, ureter and bladder) was extracted, and scored on a five-point scale for renal dilation, ureteral dilation and hydronephrosis. Whole kidney sections underwent immunohistochemistry to quantify levels of macrophages (CD68), activated fibroblasts [α-smooth muscle actin (α-SMA)], collagen (Masson's Trichrome) and Hematoxylin and Eosin. Change in renal pelvis diameter and the number of glomeruli in the treated and contralateral urinary tract was also computed.
Intrasurgical IRE performed with non-invasive caliper electrodes resulted in immediate loss of peristalsis in the treated ureteral segment, and cell death in the ureteral muscularis along with urothelial sloughing. Dilation of the ureter was observed on gross anatomic evaluation and histopathology. Magnetic resonance imaging indicated partial stricture and urinary obstruction in IRE-treated urinary tract, without evidence of urinoma, leakage or fistula formation. Enlargement of the kidney with progressive renal dilation and hydronephrosis was evident between Day 2 and Day 10 post-treatment. Obstructed kidney demonstrated scarring with elevated levels of tissue collagen, macrophages and α-SMA-positive fibroblasts. There was a steady decrease in the number of glomeruli in the obstructed kidney, while glomeruli numbers in the contralateral kidney remained unchanged through the 10-day observation period.
IRE provides a safe and reproducible technique to induce partial ureteral obstruction and renal fibrosis in rat model without the need for ligation or its associated complications.
不可逆电穿孔（IRE）使用微秒长的电脉冲通过细胞膜通透性杀死细胞，而不影响周围的细胞外结构。我们评估了 IRE 是否可用于诱导大鼠肾瘢痕模型的尿路梗阻。
在雄性大鼠的右输尿管近端进行术中 IRE（2000 V/cm，90 个脉冲，100 μs），使用卡尺电极，在手术后 2、5 或 10 天进行对比增强磁共振成像。提取整个泌尿道（双侧肾脏、输尿管和膀胱），并对肾脏扩张、输尿管扩张和肾积水进行五分制评分。对整个肾脏切片进行免疫组织化学染色，以定量检测巨噬细胞（CD68）、活化的成纤维细胞[α-平滑肌肌动蛋白（α-SMA）]、胶原（马松三色）和苏木精和伊红的水平。还计算了处理和对侧泌尿道中肾盂直径和肾小球数量的变化。
使用非侵入性卡尺电极进行的术中 IRE 导致处理输尿管段的蠕动立即丧失，并且输尿管肌层中的细胞死亡以及尿路上皮脱落。大体解剖评估和组织病理学显示输尿管扩张。磁共振成像显示 IRE 治疗的泌尿道存在部分狭窄和尿路梗阻，没有尿囊肿、泄漏或瘘管形成的证据。治疗后 2 至 10 天，肾脏逐渐扩张和肾积水导致肾脏增大。梗阻肾脏表现出疤痕形成，组织胶原、巨噬细胞和α-SMA 阳性成纤维细胞水平升高。在梗阻肾脏中，肾小球数量持续减少，而在对侧肾脏中，肾小球数量在 10 天的观察期内保持不变。
IRE 为在大鼠模型中诱导部分输尿管梗阻和肾纤维化提供了一种安全且可重复的技术，无需结扎及其相关并发症。
