Akt介导炎症反应参与顺铂诱导的急性肾损伤

目的 目前急性肾损伤（acute kidney injury,AKI）发病率和死亡率较高,尤其是肾毒性药物所致AKI更加常见,为了更好地理解和干预AKI,本实验拟研究顺铂诱发的小鼠AKI的潜在发病机制.方法 在小鼠成功构建顺铂诱发的AKI模型基础上,将10只雄性C57BL/6（25-30）克小鼠随机分为2个组,每组6只（n=6）,分为对照组和顺铂诱导的急性肾损伤模型组.模型组腹腔注射顺铂20 mg/kg,对照组腹腔注射生理盐水（20mg/kg）,顺铂或生理盐水注射72 h后处死小鼠,收集小鼠血清和肾脏标本.测定血清肌酐（SCr）和血尿素氮（BUN）.PAS染色后显微镜下观察肾脏形态学变化,Western blotting免疫蛋白印迹分析蛋白激酶B（Akt）和磷酸化蛋白激酶B（p-Akt）的表达,实时定量（RT-PCR）检测白介素-6（IL-6）,干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNF-a）.结果 与对照组相比,模型组SCr和BUN均明显升高,病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎症细胞浸润明显增加.Western blotting免疫蛋白印迹结果显示pAkt表达明显上调,Akt表达不变,RT-PCR检测显示IL-6,IFN γ和TNFα明显上调.结论 在顺铂导致的小鼠急性肾损伤模型中,Akt的激活通过介导炎症反应参与了顺铂诱导的小鼠急性肾损伤.

Involvement of Akt-mediated inflammation in cisplatin-induced acute kidney injury

Objective To explore the potential mechanism of acute kidney injury （AKI） induced by cisplatin in mice.Methods Six male C57BL/6 mice （weighing 2530 g） were randomly divided into two groups：control group,and cisplatin-induced AKI group.These mice were killed at 72nd h after administration of cisplatin injection or saline injection （20 mg/kg,i.p.）.The blood samples were collected and measured for the levels of serum creatinine （SCr） and blood urea nitrogen （BUN）.The pathologic changes of renal tissues were observed according to PAS staining.The mRNA levels of IL-6,IFN-γ and TNF-α were detected by RT-PCR.The expression of Akt and p-Akt was examined by Western blotting.Results As compared with control group,the levels of SCr and BUN in AKI group were significantly increased.Renal tubular necrosis,protein cast,and inflammatory cells infiltration in AKI group were markedly deteriorated,moreover the mRNA levels of IL-6,IFN-γand TNF-α and the expression of p-Akt were significantly up-regulated in AKI group as compared with control group.But there was no significant difference in the expression of Akt between the two groups.Conclusions Akt activation mediates inflammation in cisplatin-induced AKI.0 .