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 injury,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(10 mg·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CDDP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 , Bcl2 , 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( P ＜0.01 )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( P＜0.01 ).Conclusions NAC may prevent kidney from CDDP impairment via the p38 MAPK pathway.
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