碘克沙醇对于肾功能不全大鼠肾损伤分子-1水平及肾小管上皮细胞凋亡率的影响

The impact of Iodixanol against kidney injury molecule-1 and the renal tubular cell apoptosis in rats with renal insufficiency

目的碘克沙醇对于肾功能不全大鼠肾损伤分子-1（kidney injury molecule-l,KIM-1）及肾小管上皮细胞凋亡率的干预研究。方法将48只Wistar雄性大鼠随机分为正常对照组,模型组,碘克沙醇组1、碘克沙醇组2（n=12）。模型组与碘克沙醇组均采用右肾切除及左肾动脉缩窄法制作肾损伤模型。分别在术前、术后2周内隔日经内眦静脉取血测定BUN、SCr及取尿测KIM-1值。术后第3周对模型组静脉注射生理盐水,碘克沙醇组1注射碘克沙醇（5 mL/kg）碘克沙醇组2注射碘克沙醇（10 mL/kg）,观察碘克沙醇组在应用对比剂前与应用对比剂后3 h、24 h、48 h、72 h、7 d血尿素氮、肌酐和尿KIM-1的变化;术后第24 h、72 h、第7天,每组随机选取3只大鼠处死。采取TUNEL法测定并比较这四组动物的肾小管上皮细胞凋亡率。结果 （1）与对照组相比,模型组血清BUN、SCr水平于术后第2天急剧升高（P〈0.01）,达术前2倍左右。之后逐步下降,手术后2周时稳定于术前1.5～2.0倍水平,但尿KIM-1无显著变化（P＞0.05）。（2）与模型组相比,碘克沙醇组2在注射后24 h、72 h、第7天BUN、SCr、KIM-1、肾小管上皮细胞凋亡率明显升高（P〈0.01）,碘克沙醇组2尿KIM-1水平在碘克沙醇注射后3 h即升高,明显早于碘克沙醇组1的升高,差异具有显著性（P〈0.01）。结论通过采用左肾动脉缩窄及右肾切除的方法能制备慢性轻中度肾衰竭动物模型;碘克沙醇可引起慢性肾衰竭动物的急性肾损伤,具体机制可能和该对比剂诱导肾小管上皮细胞凋亡有关。KIM-1能作为对比剂肾病的早期预测指标。不同浓度的对比剂对肾小管的损伤作用是不同的。

Objective To observe the impact of Iodixanol against kidney injury molecule-1 and the renal tubular cell apoptosis in rats with renal insuffi ciency. Methods 48 male wistar rats were randomly divided into four groups： normal control group, model group, Iodixanol group1, Iodixanol group2（n=12）. Iodixanol groups and model group were applied the methods of left renal artery narrowing（30%）, right nephrectomy to produce renal insuffi ciency model in rats respectively, in the preoperative and postoperative 2 weeks every other day by measuring the angular vein blood BUN, SCr and taking urine test of urinary kidney injury molecule-1（KIM-1） values. After the fi rst three weeks of intravenous saline model group, iodixanol（5 mL/kg）injection of iodixanol group 1, iodixanol（10 mL/kg）injection of iodixanol group 2, the changes of blood urea nitrogen, creatinine and urinary KIM-1 of the two iodixanol groups before applying the contrast agent, after 3 h, 24 h, 48 h, 72 h and 7 d were observed. Three rats of each group were sacrifi ed in 24 h, 72 h and 7th day after injection of contrast agent. The renal tubular cell apoptosis rates were measured by TUNEL and the differences of each group were compared. Results After in the fi rst two days of surgery, serum BUN, SCr levels in model group were signifi cantly higher than that of the normal group（P〈0.01） and rised sharply up to about 2 times before surgery, Then gradually decreased after surgery stable at 1.5-2.0 times the preoperative levels two weeks. But the values of KIM-1 were no signifi cant difference（P〉0.05）. Compared with the model group, in 24 h, 72 h and 7th day after the injection of contrast agents, the values of BUN and SCr, the value of KIM-1 in urine and the rates of apoptosis of renal tubular cells in iodixanol group 2 were signifi cantly increased higher than that of the model group（P〈 0.01）. After three hours iodixanol injection of iodixanol group 2, urinary KIM-1 levels that increased signifi cantly earlier than the rise in the iodixanol group1, the difference was signifi cant（P〈 0.01）. Conclusion By using the left renal artery narrowing and right nephrectomy method can be prepared with mild to moderate chronic renal failure in animal models; iodixanol can cause acute kidney injury of chronic renal failure animals and the specifi c mechanisms may induce renal contrast agent tubule epithelial cell apoptosis. KIM-1 can be used as a contrast agent nephropathy early predictors. Different concentrations of contrast agents for renal tubular injury are different.