肾组织细胞凋亡在脓毒症诱发小鼠急性肾损伤中的作用

目的 探讨肾组织细胞凋亡在脓毒症诱发小鼠急性肾损伤中的作用.方法 健康清洁级雄性C57BL/6小鼠45只,随机分为3组(n=15),假手术组(S组)、盲肠结扎穿孔术组(CLP组)和半胱氨酸蛋白酶(caspase)-3抑制剂+盲肠结扎穿孔术组(CI组),CLP组于术前30 min时腹部皮下注射caspase-3抑制剂Ac-DEVD-CHO 4μg/g.分别于CLP术后6、12、24 h时取眼球法采集血样,测定血清尿素氮(BUN)和肌酐(Cr)的浓度,然后取肾组织,测定细胞凋亡情况、caspase-3蛋白和caspase-3 mRNA表达水平,光镜下观察肾组织病理学结果.结果 与S组比较,CLP组血清BUN、Cr的浓度及肾组织细胞凋亡率升高,caspase-3 mRNA表达上调(P＜0.05),caspase-3蛋白表达上调;与CLP组比较,CI组血清BUN、Cr的浓度及肾组织细胞凋亡率降低,caspase-3 mRNA表达下调(P＜0.05),caspase-3蛋白表达下调.CI组肾组织病理学损伤程度轻于CLP组.结论 肾组织细胞凋亡是脓毒症诱发小鼠急性肾损伤的机制之一.

Role of renal cell apoptosis in acute kidney injury induced by sepsis in mice

Objective To evaluate the role of renal cell apoptosis in acute kidney injury (AKI) induced by sepsis in mice. Methods Forty-five male C57BL/6 mice were randomly assigned into 3 groups ( n = 15 each):sham operation group (group S), cecum ligation and puncture group (group CLP) and CLP + caspase-3 inhibitor Ac-DEVD-CHO group (group CI). Intra-abdominal infection was induced by CLP. Ac-DEVD-CHO 4 μg/g was infused subcutaneously 30 min before CLP in group CI. Five mice in each group were sacrificed after collection of blood samples at 6, 12 and 24 h after CLP. The levels of serum blood urea nitrogen (BUN) and creatinine (Cr)were detected. The apoptosis rate and expression of caspase-3 protein and caspase-3 mRNA were determined.Pathological changes in renal tissues were observed with light microscope. Results The serum BUN and Cr concentratiors, apoptosis rate and expression of caspase-3 mRNA and caspase-3 protein were significantly higher in group CLP than in group S, but lower in group CI than in group CLP ( P ＜ 0.05). Light microscopic examination showed that the pathologic changes induced by Ac-DEVD-CHO were less severe in group CI than in group CLP.Conclusion The renal cell apoptosis is one of the mechanism of AKI induced by sepsis.