Biph硝普钠对大鼠肾组织块细胞增生及蛋白合成的双向性作用以及环鸟核苷酸环化酶特异性抑制剂 ODQ对其影响(英文)

Biphasic Effects of Sodium Nitroprusside on Cell Proliferation and Protein Synthesis in Rat Kidney Slices-Influence of Specific Cyclic Guanylyl Cyclase Inhibitor-ODQ

目的 :探讨一氧化氮 ( NO)对孵育的肾组织块细胞增生和蛋白合成的影响。方法 :取正常 Wistar大鼠肾组织块 4 0 -70 mg,置于 Krebs-Henseleit溶液中 ,放入 37℃恒温并带有摇床 (频率 1 0 0次 /分 )的孵育箱中孵育 2 h,孵育液中持续通入混合氧 ( O2 ∶CO2 =95∶ 5)。细胞增生和蛋白合成分别采用 [3H]-胸腺嘧啶和 [1 4 C]-亮氨酸掺入法测定。结果 :本研究结果显示 ,低浓度硝普钠 ( SNP,0 .5μmol·L- 1 )分别引起 [3H]-胸腺嘧啶和 [1 4C]-亮氨酸掺入增加 ( P<0 .0 1 ) ,而高浓度 SNP( 50～ 50 0 μmol·L- 1 )显著抑制 [3H]-胸腺嘧啶和 [1 4 C]-亮氨酸掺入 ( P<0 .0 1 )。 ODQ ( 1 -H-[1 ,2 ,4 ]oxadiazolo[4 ,3-a]quinoxalin-1 -one)可显著防止 SNP对 [3H]-胸腺嘧啶和 [1 4C]-亮氨酸掺入的刺激作用 ( P<0 .0 1 ) ,而对高浓度 SNP所导致的 [3H]-胸腺嘧啶和 [1 4 C]-亮氨酸掺入抑制作用无影响。结论 :本研究结果提示 NO对肾脏细胞增生和蛋白合成有双向性调节作用 ,其刺激作用可能由 c GMP介导。

AIM: To investigate the role of nitric oxide (NO) on cell proliferation and protein synthesis of the incubated kidney slices. METHODS: Kidney slices weighing 40~70 mg from normal Wistar rats were incubated with Krebs Henseleit solution at 37℃ with 100 cycles/min shaking for 2 hours and continuously oxygenized by the mixed O 2 (O 2∶CO 2=95∶5). Cell proliferation and protein synthesis were determined by measuring the [ 3H]thymidine and [ 14 C]leucine incorporation respectively. RESULTS: It was shown that the lower concentration of sodium nitroprusside (SNP, 0.5 μmol/L) exerted a stimulatory effect on [ 3H]thymidine and [ 14 C]leucine incorporation ( P <0.01, respectively), while the higher concentrations of SNP (50~500 μmol/L) exerted an inhibitory effect on [ 3H]thymidine and [ 14 C]leucine incorporation ( P <0.01, respectively). ODQ (1 H [1,2,4]oxadiazolo[4,3 a]quinoxalin 1 one) could prevent the stimulatory effect of low dose SNP induced [ 3H]thymidine and [ 14 C]leucine incorporation ( P <0.01, respectively) rather than the inhibitory effect induced by high dose of SNP. CONCLUSION: NO might exert biphasic effects on cell proliferation and protein synthesis to the kidney, and its stimulatory effect may be mediated by cGMP.