一氧化氮合酶在急性环孢素A肾中毒中的变化及意义

Effect of Cyclosporine A on NOS Activity in Rat Kidney

目的 探讨大鼠急性环孢素 A(Cs A)肾中毒时一氧化氮合酶 (NOS)的变化及其意义。方法 健康雄性 SD大鼠4 8只随机分为 4组 :Gl为对照组 ;G2组以 Cs A 5 0 mg· kg- 1 灌胃 ;G3组以 Cs A5 0 m g· kg- 1 +L -精氨酸 (L - arg,3 0 0 m g·kg- 1 )灌胃 ;G4组以 Cs A5 0 mg· kg- 1 +L-硝基精氨酸甲基酯 (L- NAME,5 mg· kg- 1 )灌胃。结果 实验至第 7天末 ,G4组肾组织匀浆 NOS活性明显降低 ,G1、G2、G3组间 NOS活性差异无统计学意义 ;G2组有明显肾中毒表现 ,G3组肾损害较 G2、G4组减轻 ;G3组尿内 NO- 2 /NO- 3 明显增加 ,G4组尿内 NO- 2 /NO- 3 的排出减少 ,P<0 .0 5。光镜检查发现 G2组近曲小管上皮细胞空泡变性 ,上皮细胞胞浆脱落 ,尤以皮髓交界处较为明显 ,肾小管管周细胞浸润 ,血管充血。 G4组 Cs A肾损害加重 ,G3组Cs A肾病理改变减轻。结论 大剂量 Cs A体内应用对大鼠肾 NOS活性可能无抑制效应 ,L - arg对 Cs A所致肾毒性有拮抗作用 ,小剂量 L- NAME对 Cs

Objective To evaluate the effect of in vivo administration CsA on NOS activity in rat kidney. Methods Four groups of male Sprague Dawley rats were treated with daily gavage for seven days: Gl: control, G2: CsA 50 mg/kg, G3: CsA 50 mg/kg+L arg 300 mg/kg, G4: CsA 50 mg/kg+LNAME 5 mg/kg. Results After 7 days L arg treated rats were protected against the toxic effects of CsA. In contrast, administration of LNAME strikingly worsen the renal function and reduced urinary NO production. Urinary NO metabolites NO - 2/NO - 3, determined by Griess reaction, were much higher in G3 than other groups, while the difference between Gl and G2 is not significant statistically. NOS activity, assayed by measuring methyl haemoglobin in kidney homogenates, was blocked in G4, and showed no significant difference among other groups. Light microscopy demonstrated toxic tubulopathy, peritubular capillary congestion and interstitial edema in G2. The degree of renal tissue change in G4 was the most severity. G3 had mild renal tissue changes. Conclusion CsA, large dose in vivo administration, may not suppress NOS activity in rat kidnmy. Acute CsA nephrotoxicity can be aggravated by L NAME, and ameliorated by NO precursor L arg.