吡咯烷二巯基氨甲酸对大鼠肾缺血再灌注的保护作用及机制

目的 探讨吡咯烷二巯基氨甲酸(PDTC)对大鼠肾缺血再灌注的保护作用及可能的机制.方法 选择成年、健康及雄性的Wistar大鼠56只,随机分为缺血再灌注损伤(IRI)组,PDTC组及对照组.IRI组:24只,建立大鼠肾缺血再灌注模型;PDTC组:24只,缺血再灌注前15 min经鼠尾静脉注射PDTC 150 mg/kg,其余步骤同IRI组;对照组:8只,不给予缺血再灌注处理.IRI组和PDTC组分别于再灌注后2、6和24 h检测大鼠血清肌酐(Cr)和尿素氮(BUN)水平;检测肾组织中自细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)的含量;逆转录聚合酶链反应(RT-PCR)检测肾组织中核因子-κB(NF-κB)和诱导型一氧化氮合酶(iNOS)mRNA表达水平;苏木素-伊红(HE)染色观察大鼠肾组织的病理变化.取对照组的各项数据作为正常对照.结果 IRI组大鼠再灌注后各时间点的血Cr、BUN、IL-8及TNF-α含量、NF-κB和iNOS mRNA表达水平均高于对照组和PDTC组(P<0.05).再灌注后6 h时,PDTC组大鼠肾组织中IL-8和TNF-α含量与对照组比较,差异无统计学意义(P>0.05).再灌注后24 h时,PDTC组大鼠各项生化指标与对照组相比,差异均无统计学意义(P>0.05).PDTC组大鼠肾损伤的病理变化较IRI大鼠明显减轻.结论 PDTC通过抑制NF-κB,有效减少IL-8,TNFα和iNOS的产生,对肾缺血再灌注有良好的保护作用.

Protective effect of pyrrolidine dithiocarbamate on the rat kidney from ischemia reperfusion injury

Objective To investigate the protective mechanism of pyrrolidine dithiocarbamate (PDTC) on the kidney in the isehemia-reperfusion injury model (IRI).Methods Fifty-six health adult Wistar rats were randomly divided into three groups: IRI group (n = 24), PDTC group (n = 24, 150 mg/kg PDTC was administered before IRI), and control group (n = 8).Rats in IRI and PDTC groups were sacrificed at the 2nd, 6th and 24th h after IRI.Serum levels of urea nitrogen (BUN) and creatinine (Cr) were determined.Levels of IL-8, TNF-α, NF-κB and iNOS mRNA was detected in renal tissues.Histological changes were observed.Results At the 2nd, 6th and 24th h after IRI, levels of BUN, Cr, IL-8, TNF-α, NF-κB and iNOS mRNA in IRI group were increased significantly as compared with control and PDTC groups (P<0.05).There was no significant difference in the contents of IL-8 and TNF-α between control and PDTC groups at the 6th h after IRI (P>0.05).No significant differences were found in all parameters between PDTC and control groups at the 24th h after IRI (P>0.05).In comparison to Irl group, renal pathological changes in PDTC group were alleviated significantly.Conclusion These findings indicate that PDTC pretreatment obviously attenuates IRI by down-regulating IL-8, TNF-α and iNOS through inhibiting NF-κB.