碘普罗胺联合禁水建立造影剂肾病大鼠模型及细胞凋亡表现

The establishment of contrast nephropathy rat model by ioprolamine combined with water deprivation and the expression of apoptosis

目的建立造影剂直接肾脏损伤的动物模型,通过综合指标判断模型成功,为造影剂肾病研究提供模型借鉴。方法对SD大鼠行禁水联合静脉给予含碘造影剂,通过检测肾损伤标志物变化,同时观察肾组织形态学及细胞凋亡改变得到较好的疾病表型。结果单纯禁水组在恢复饮水24h后检测肌酐、尿素氮水平几乎恢复基线值,而禁水联合造影剂组术后血清肌酐可观察到明显升高(54.45±14.39μmol/L vs.28.26±9.98μmol/L;P<0.01),尿素氮水平也持续升高(34.70±2.66μmol/L vs.10.75±5.45μmol/L;P<0.001)。HE染色提示造影剂肾病建模组组织受损主要集中在肾皮髓交界、外髓内带的近端小管;表现为小管上皮细胞空泡样变性,细胞扁平萎缩或坏死脱落,损伤评分差异显著(2.0±0.82 vs.0.46±0.49;P=0.02)。同时凋亡蛋白Bax在e组(禁水+造影剂)(P=0.02)及f组(禁水+速尿+造影剂)较对照组表达明显升高(P=0.015);TUNEL法检测细胞凋亡率在e组(16.2±5.2%vs.5.1±1.3%;P<0.01)及f组较对照组均明显增加(20.8±8.7%vs.5.1±1.3%;P<0.001)。结论利用综合指标分析评估,直接造影剂接触联合禁水预处理方法能稳定的建立造影剂肾病模型。

Objective To establish the animal model of direct renal injury by contrast medium,and provide the model reference for the study of contrast medium nephropathy.Methods SD rats were given iodized contrast media by water deprivation combined with intravenous administration.The better disease phenotype was obtained by detecting the changes of renal injury markers and observing the changes of renal histomorphology and apoptosis.Results The serum creatinine and urea nitrogen levels were almost restored to the baseline value in the water control group after drinking water for 24 hours,but the serum creatinine level in the water control group was significantly increased(54.45±14.39μmol/L vs.28.26±9.98μmol/L;P<0.01)and the urea nitrogen level was also continuously increased(34.70±2.66μmol/L vs.10.75±5.45μmol/L;P<0.001).HE staining showed that the damage of the tissue in the model group was mainly concentrated in the proximal tubules at the junction of renal cortex and medulla and in the outer medulla,which showed vacuolar degeneration of tubule epithelial cells,flat atrophy or necrosis of cells.The difference of damage score was significant(2.0±0.82 vs.0.46±0.49;P=0.02).At the same time,the expression of apoptotic protein Bax was significantly increased in group e(P=0.02)and group f compared with the control group(P=0.015).Apoptosis rate in group e(16.2±5.2%vs.5.1±1.3%;P<0.01)and group f were significantly increased compared with the control group(20±8.7%vs.5.1±1.3%;P<0.01).Conclusion Sing the comprehensive index analysis and evaluation,direct contrast agent contact combined with water deprivation pretreatment method can establish a stable contrast agent nephropathy model.