目的：探讨新生大鼠内毒素血症时肾脏损害的部分机制及地塞米松(Dex)的干预作用。方法：取7日 Wistar大鼠150只，随机分为A组(对照组)：等体积生理盐水腹腔注射；B组(LPS组)：内毒素(LPS)5 mg/kg腹腔注射制成内毒素血症模型；C组(治疗组)：LPS 5 mg/kg+Dex 5 mg/kg共同腹腔注射。各组于注射前(0 h)及注射后2，4，6，24 h分别断头处死留取肾脏。肾组织一氧化氮(NO)采用硝酸还原酶法测定，肾组织一氧化氮合酶(NOS)采用底物催化法测定，通过电镜观察肾脏超微结构变化。结果：①B组NO于2 h高于A组同时间点NO浓度(1.69±0.44 nmol/mg vs 1.20±0.36 nmol/mg)，差异有显著性(P<0.05)。于24 h为同时间点A组的 2.3倍(3.12±0.41 nmol/mg vs 1.35±0.38 nmol/mg)，差异有显著性(P<0.01)；C组NO也于2 h明显高于A组同时间点NO浓度(1.63±0.27 nmol/mg vs 1.20±0.36 nmol/mg)，(P<0.05)，但于24 h升高程度低于B组(2.10±0.27 nmol/mg vs 3.12±0.41 nmol/mg) (P<0.05)；②B组肾NOS于2 h明显高于A组同时间点NOS浓度(0.47±0.15 U/ml vs 0.38±0.12 U/ml) (P<0.05)，于4 h短暂下降后于24 h明显高于同时间点A组NOS浓度(0.65±0.27 U/ml vs 0.38±0.15 U/ml) (P<0.05)；C组NOS浓度自6 h逐渐升高，至24 h均明显低于B组 0.51±0.07 U/ml vs 0.65±0.27 U/ml) (P<0.05)；③电镜下A组肾小球基底膜(GBM)完整，上皮细胞足突清晰，肾小管上皮细胞完整，可见刷状缘。B组6 h肾小球GBM完整，部分上皮细胞足突融合，肾小管上皮细胞线粒体空泡变性；24 h肾小球GBM断裂，上皮细胞足突明显融合，系膜细胞线粒体嵴断裂，空泡变性。肾小管上皮细胞线粒体扩张成大泡。C组24 h肾小球GBM基本正常，上皮细胞足突部分轻度融合，系膜细胞内少数线粒体空泡变性，肾小管可见刷状缘。 结论：新生鼠内毒素血症时肾脏NOS产生增加，诱导合成过量的NO参与肾损伤。Dex通过调节肾脏NOS而抑制NO的大量合成，具有肾脏保护作用。

OBJECTIVE: To study the mechanism of the kidney injury and the protective effect of dexamethasone (Dex) on kidneys in neonatal rats with endotoxemia. METHODS: One hundred and fifty 7-day-old newborn Wistar rats were randomly assigned into 3 groups: a LPS group, a Dex group and a Control group. The LPS group was injected intraperitoneally by a single bolus of lipopolysaccharide (LPS, 5 mg/kg). The Dex group received an injection with LPS 5 mg/kg plus Dex 5 mg/kg. The Control group received the same volume of 0.9% sodium chloride as the other two groups. The rats were sacrificed at 0, 2, 4, 6, 24 hrs of post-infection (10 rats each). The nitric oxide (NO) levels in kidneys were measured by colorimetric analysis. The nitric oxide synthase (NOS) concentrations of the kidney were measured by the biochemical method. The superstructure of the kidney was observed under the electron microscope. RESULTS: The NO levels of the kidneys in the LPS group were higher than those of the Control group at 2 hrs of post-injection ( 1.69± 0.44 nmol/mg vs 1.20± 0.36 nmol/mg; P< 0.05), increasing to be 2.3 times greater than the Control group at 24 hrs ( 3.12± 0.41 nmol/mg vs 1.35± 0.38 nmol/mg; P< 0.01). The NO levels of the Dex group ( 1.63± 0.27 nmol/mg) were also higher than those of the Control group at 2 hrs (P< 0.05), while they were lower than those of the LPS group at 24 hrs ( 2.10± 0.27 nmol/mg; P< 0.05). The NOS contents of the kidneys at 2 hrs of post-injection ( 0.47± 0.15 U/ml) and at 24 hrs ( 0.65± 0.27 U/ml)in the LPS group were both higher than those of the Control group ( 0.38± 0.12 U/ml and 0.38± 0.15 U/ml; both P< 0.05). The NOS content elevated at 6 hrs in the Dex group compared with that of the Control group, but it was lower than that of the LPS group at 24 hrs ( 0.51± 0.07 U/ml vs 0.65± 0.27 U/ml; P< 0.05). Under the electron microscope, the complete renal glomerulus GBM and clear epithelial cell foot processes were found, and the complete renal tubule epithelial cells and brush border were also found in the Control group. In the LPS group, renal glomerulus GBM was fractured, epithelial cell foot processes had obvious confluence, a great quantity of mesangial cells mitochondria presented vacuolation, and renal tubules epithelial cell mitochondria were expanded to bubbles at 24 hrs of post-injection. In the Dex group, renal glomerulus GBM almost recovered to normal, partial epithelial cell foot processes were slightly fused, and a small quantity of mitochondria vacuolation in mesangial cells and the brush border in renal tubules were found at 24 hrs of post-injection. CONCLUSIONS: LPS can stimulate the kidneys to produce more NOS which induces to synthesize excessive NO in neonatal rats. Dex can protect kidneys from NO damage by inhibiting the NOS production and yielding a decrease of the NO level.