乌司他丁对缺血性急性肾损伤大鼠肾功能及肾损伤因子-1水平的影响

Effects of ulinastatin on renal function and renal injury factor-1 level in rats with ischemic acute kidney injury

目的探讨乌司他丁对缺血性急性肾损伤(IAKI)大鼠肾功能及肾损伤因子-1(KIM-1)水平的影响。方法用结扎输尿管法建立IAKI模型。将模型大鼠随机分为模型组和实验组,每组10只;另取10只正常大鼠作为假手术组。术后,假手术组和模型组均给予尾静脉推注3 mL·kg^(-1)·d^(-1)0.9%NaCl;实验组给予尾静脉推注3.0×10^(4) U·kg^(-1)·d^(-1)乌司他丁。3组大鼠均每天给药1次,连续给药7 d。用酶联免疫吸附实验法检测大鼠肾功能,用实时荧光定量聚合酶链反应法检测磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(AKT)mRNA的表达水平。结果实验组、模型组和假手术组的血清肌酸酐分别为(71.36±10.31),(108.23±16.36)和(48.15±5.65)μmol·L^(-1),尿素分别为(13.54±3.42),(21.80±5.65)和(8.37±3.03)mmol·L^(-1),KIM-1分别为(1.74±0.18),(2.48±0.34)和(1.10±0.12)μg·L^(-1),肾组织中PI3K mRNA相对表达量分别为1.68±0.14,2.28±0.26和1.00±0.00,肾组织中AKT mRNA相对表达量分别为1.49±0.13,2.16±0.19和1.00±0.00,模型组的上述指标与实验组和假手术组比较,差异均有统计学意义(均P<0.05)。结论乌司他丁对IAKI大鼠有肾保护作用,其可通过调控PI3K/AKT信号通路,抑制肾小管细胞凋亡,进而改善肾损伤。

Objective To explore the effects of ulinastatin on renal function and the level of kidney injury factor-1(KIM-1)in rats with ischemic acute kidney injury(IAKI).Methods The model of IAKI was established by ligation of ureter.Model rats were randomly divided into model and experimental groups with 10 rats per group.Another 10 normal rats were selected as the sham-operation group.Postoperatively,the sham-operation and model groups were given 3 mL·kg^(-1)·d^(-1)0.9%NaCl through caudal vein.The experimental group was injected with 3.0×10^(4) U·kg^(-1)·d^(-1) ulinastatin via caudal vein.Three groups were administered once a day for consecutive 7 d.The renal function of the rats was determined by enzyme-linked immunosorbent assay.The expression levels of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)mRNA were determined by real-time fluorescence quantitative polymerase chain reaction.Results The serum creatinine of experimental,model and sham-operation groups were(71.36±10.31),(108.23±16.36)and(48.15±5.65)μmol·L^(-1),urea were(13.54±3.42),(21.80±5.65)and(8.37±3.03)mmol·L^(-1),KIM-1 were(1.74±0.18),(2.48±0.34)and(1.10±0.12)μg·L^(-1),the relative expression levels of PI3K mRNA in renal tissue were 1.68±0.14,2.28±0.26 and 1.00±0.00,the relative expression levels of AKT mRNA in renal tissue were 149±0.13,2.16±0.19 and 1.00±0.00.The differences were statistically significant between model group and experimental,sham-operation groups(all P<0.05).Conclusion Ulinastatin has renal protective effect on rats with IAKI,which can inhibit renal tubular cell apoptosis by regulating PI3K/AKT signaling pathway,thus improving renal injury.