Department of Nephrology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8916-8922. doi: 10.3892/mmr.2017.7692. Epub 2017 Oct 3.
The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl‑2 (Bcl‑2) and caspase‑3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase‑3 levels were increased, and the expression of Bcl‑2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase‑3 levels significantly decreased, and the expression of Bcl‑2 was restored (P<0.05). UTI inhibited renal tubular epithelial apoptosis and interstitial fibrosis in UUO rats.
乌司他丁对单侧输尿管梗阻（UUO）大鼠肾小管上皮细胞凋亡和间质纤维化的影响。雄性 Wistar 大鼠 18 只，随机分为 3 组：假手术组（n=6）、UUO 组（n=6）和乌司他丁组（n=6）。UUO 组和乌司他丁组结扎左侧输尿管，建立 UUO 模型。术后第 1 天开始，分别用生理盐水（1ml/kg/d）和乌司他丁（40000 单位/kg/d）进行干预治疗。术后第 7 天每组处死 6 只大鼠。假手术组仅游离左侧输尿管，不结扎。术后第 7 天关腹，所有大鼠均处死。处死动物前采集血样，检测血尿素氮（BUN）和血清肌酐（Scr）。苏木精-伊红和 Masson 染色观察梗阻侧肾间质病变发生率。末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色和凋亡调控因子 Bax（Bax）、凋亡调控因子 Bcl-2（Bcl-2）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）免疫组化检测观察肾小管上皮细胞凋亡情况。乌司他丁对各组小鼠 BUN 和 Scr 水平均无明显影响（P>0.05）。与假手术组相比，UUO 组肾小管扩张，上皮细胞萎缩，肾间质炎症细胞浸润，纤维组织增生，肾组织损伤明显加重（P<0.01）。肾小管上皮 TUNEL+细胞数、Bax 和 caspase-3 水平升高，Bcl-2 表达降低（P<0.01）。乌司他丁治疗后，梗阻侧肾间质损伤明显减轻（P<0.05），肾小管上皮 TUNEL+细胞数、Bax 和 caspase-3 水平降低，Bcl-2 表达恢复（P<0.05）。乌司他丁抑制 UUO 大鼠肾小管上皮细胞凋亡和间质纤维化。
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