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目的研究乌司他丁(Ulinastatin,UTI)对造影剂肾毒性大鼠肾小管上皮细胞凋亡和凋亡相关基因半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白表达的影响。方法将大鼠随机均分为正常组、模型组、UTI低、高剂量组(2.5×104、5.0×104IU·kg-1)。除正常组外,其余各组均于大鼠后腿深部肌肉注射25%甘油(10 m L·kg-1),48 h后于尾静脉iv 76%泛影葡胺(10m L·kg-1)造模。UTI组大鼠分别在注射造影剂24、48 h后给药,测定血清中胱抑素C(Cys C)和肌酐(Scr)的水平;光镜下观察肾组织的病理学变化,进行Paller评分;TUNEL染色检测肾小管上皮细胞的凋亡;免疫组化法检测Caspase-3蛋白的表达。结果模型组大鼠的肾小管上皮细胞出现明显水肿、空泡变性和颗粒变性、刷状缘丢失以及肾小管扩张等;与正常组比较,模型组的血清Cys C和Scr水平、Paller评分显著升高,肾小管上皮细胞凋亡增多,Caspase-3蛋白表达显著上调,与模型组比较,UTI组的血清Cys C、Scr水平明显降低,肾组织损害减轻、Paller评分下降,肾小管上皮细胞Caspase-3蛋白的表达显著下调,细胞凋亡率明显降低。结论 UTI可下调大鼠肾小管上皮细胞Caspase-3蛋白的表达,抑制肾小管上皮细胞的凋亡,对造影剂肾毒性大鼠起保护作用。
Objective To investigate the effects of Ulinastatin on renal tubular epithelial cells apoptosis and the expression of caspase-3 protein in nephrotoxic rats. Methods The rats were randomly divided into normal group, model group, low and high UTI group (2.5 × 104, 5.0 × 104IU · kg-1). Except for the normal group, rats in the other groups were intramuscularly injected with 25% glycerol (10 m L · kg -1) Modeling. The rats in UTI group were injected with contrast medium 24 h and 48 h after injection, respectively. Serum levels of Cystatin C and Scr were measured. The pathological changes of renal tissues were observed under light microscope and the Paller score TUNEL staining was used to detect the apoptosis of renal tubular epithelial cells; immunohistochemistry was used to detect the expression of Caspase-3 protein. Results The rat model of renal tubular epithelial cells showed obvious edema, vacuolar degeneration and granular degeneration, brush edge loss and tubular dilatation; compared with the normal group, the model group serum Cys C and Scr levels, Paller score significantly increased The expression of Caspase-3 protein in UTI group was significantly lower than that in UTI group. The levels of Cys C and Scr in UTI group were significantly decreased, the damage of renal tissue was alleviated, the Paller score was decreased, the expression of Caspase- 3 protein was significantly downregulated, the apoptosis rate was significantly reduced. Conclusions UTI can down-regulate the expression of Caspase-3 in rat renal tubular epithelial cells, inhibit the apoptosis of renal tubular epithelial cells and protect the nephrotoxic rats.