Abstract：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.
WU Yu-Bin,LI Yu-Jie,BAI Ying. Renal damage induced by endotoxin and the protective effect of dexamethasone on kidneys in neonatal rats[J]. CJCP, 2004, 6(4): 269-273.
