烫伤脓毒症大鼠肾脏核转录因子-kB活化与肾损伤关系的研究

目的 研究烫伤脓毒症大鼠肾脏核转录因子-kB（NF-kB）活化与肾损伤的关系。方法采用30％总体表面积Ⅲ度烫伤加内毒素攻击制备烫伤脓毒症大鼠模型。54只Wistar大鼠随机分为正常对照组、烫伤脓毒症1、2、6、12和24h组，烫伤脓毒症1、2和6h＋NF-kB抑制剂吡咯烷二硫基甲酸酯（PDTC）组。采用凝胶电泳迁移率改变分析法（EMSA）检测肾组织NF-kB活性；采用酶联免疫吸附法检测血浆及肾组织中肿瘤坏死因子-α（TNF-α）含量的变化；采用自动生化分析仪检测血肌酐（SCr）和尿素氮（BUN）含量。结果肾组织NF-kB活性于烫伤脓毒症后1h明显增强并达到高峰（P〈0．01），PDTC可显著降低烫伤脓毒症后1h NF-kB的活性。烫伤脓毒症后1h和2h血浆及肾组织中TNF-α水平均明显增高（P均〈0．01），PDTC可显著降低伤后血浆TNF-α水平（P均〈0．01），对肾组织中TNF-α水平影响不明显。烫伤脓毒症后BUN及SCr含量均明显增高（P均〈0．01），PDTC对BUN和SCr含量均无显著影响。结论NF-kB抑制剂可降低烫伤脓毒症大鼠肾组织NF-kB活性，但对肾脏功能无明显保护作用。

Relationship between nuclear factor-kB activity and kidney injury in rats with postburn sepsis

OBJECTIVE: To investigate the relationship between nuclear factor-KappaB (NF-KappaB) activity and kidney injury in rats with postburn sepsis. METHODS: Rats subjected to 30% full-thickness scald injury, followed by intraperitoneal injection of lipopolysaccharide (LPS), were used in the present study. Fifty-four Wistar rats were randomly divided into normal control group, postburn sepsis 1, 2, 6, 12, 24 hours groups, and sepsis with NF-KappaB inhibitor pyrrolidine dithiocarbamate (PDTC) treatment 1, 2, and 6 hour groups. NF-KappaB activity, tumor necrosis factor-alpha (TNF-alpha) protein expression, and renal function were determined with electrophoretic mobility shift assay (EMSA), enzyme linked immunoadsorbent assay (ELISA), and automatic biochemistry analyzer, respectively. RESULTS: NF-KappaB activity in kidney was markedly enhanced and reached its peak 1 hour after scalding and injection of LPS (all P<0.01), and was decreased remarkally after the administration of PDTC. PDTC could suppress the elevated plasma TNF-alpha protein expression (both P<0.01), but not renal TNF-alpha levels. PDTC could not reduce blood urea nitrogen and blood creatinine contents, which were increased after scalding followed by LPS challenge. CONCLUSION: The results suggest that the treatment with NF-KappaB inhibitor PDTC could down-regulate the NF-KappaB activity in kidney, but it could not protect the renal function in rats with postburn sepsis.