N-乙酰半胱氨酸影响p38有丝分裂原活化蛋白激酶对顺铂诱导急性肾损伤的保护作用

Protective effect of N-acetylcysteine on cisplatin-induced acute Kidney injury related to p38MAPK pathway in rats

目的研究N-乙酰半胱氨酸(N-acetylcysteine,NAC)对顺铂(cisplatin,CDDP)诱导大鼠急性肾损伤(acute kidney in-jury,AKI)后组织细胞凋亡的影响和与p38有丝分裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38MAPK)的关系。方法静脉注射CDDP制备大鼠AKI模型。大鼠随机分为正常对照组、AKI模型对照组、NAC低剂量组(50 mg.kg-1)、NAC中剂量组(100 mg.kg-1)、NAC高剂量组(200 mg.kg-1)、特异性p38MAPK抑制剂SB203580组(10mg.kg-1)。大鼠预先连续给药3 d,给予CDDP,再继续给药5 d。TUNEL法进行细胞凋亡检查。试剂盒测定肾脏组织caspase-3。Western blot测定caspase-3、Bax、Bcl-2、磷酸化p38MAPK(phosphorylated p38MAPK,p-p38MAPK)表达。结果与正常对照组相比,CDDP诱导AKI模型组肾组织凋亡细胞增加,caspase-3、Bax、p-p38MAPK表达升高,Bcl-2表达降低(P<0.01)。与AKI模型组相比,NAC与SB203580减少凋亡细胞、降低肾脏组织caspase-3、Bax、p-p38MAPK表达和增加Bcl-2表达(P<0.01)。结论 NAC可有效防治CD-DP诱导大鼠AKI,并与p38MAPK相关。

Aim To investigate the effects of N-acetylcysteine（NAC）on cisplatin（CDDP）-induced acute kidney injury（AKI） and its relationship with p38 mitogen activated protein kinase（p38 MAPK） pathway.Methods The rat was injected CDDP intravenously to make AKI model.The rats were randomly divided into 6 groups,including the normal control group,AKI model group,NAC 50 mg·kg-1 group,NAC 100 mg·kg-1 group,NAC 200 mg·kg-1 group and p38MAPK specific inhibitor SB203580 10 mg·kg-1 group.NAC and SB203580 were administered once a day for three days before CDDP was given.And then NAC and SB203580 were continuously given o.d.for five days.The apoptosis of kidney was monitored by TUNEL.The content of caspase-3 in kidney was determined by the commercial kit.The expression of caspase-3,Bax,Bcl-2,phosphorylated p38MAPK（p-p38MAPK）were measured by Western blot.Results Compared with the normal control group,apoptosis cells and expressions of caspase-3、Bax、p-p38MAPK in kidney were increased and the expression of Bcl-2 in kidney was decreased（P0.01）in the model group.NAC and SB203580 reduecd the apoptosis cells,supressed the expressions of caspase-3,Bax,p-p38MAPK and augmented the expression of Bcl-2 to protect kidney from CDDP injury compared with the AKI model group（P0.01）.Conclusions NAC may prevent kidney from CDDP impairment via the p38 MAPK pathway.