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

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目的:探讨—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大鼠组织块40-70mg,置于Krebs-Henseleit溶液中,放入37℃恒温并带有摇床(频率100次/分)的孵育箱中孵育2h,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[14C]-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[14C]-亮氨酸掺入增加(P<0.01),而高浓度SNP(50~500μmol·L-1)显著抑制[3H]-胸腺嘧啶和[14C]-亮氨酸掺入(P<0.01)。oDQ(1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one)可显著防止SNP对[3H]-胸腺嘧啶和[14C]-亮氨酸掺入的刺激作用(p<0.01),而对高浓度SNP所导致的[3H]-胸腺嘧啶和[14C]-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cGMP介导。“,”AIM: To investigate the role of nitric oxide (NO) on cellproliferation and protein synthesis of the incubat ed kidney slices. METHODS: Kidney slices weighing 40~70 mg from normal Wistar rats were incubated with Krebs Henseleit solution at 37 C with 100 cycles/min shaking for 2 hours and continuously oxygenized by the mixed O2(O2: CO2 =95: 5). Cell proliferation and protein synthesis were determined by measuring the [3H]thymidine and [14C]leucine in corporation 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 [14C]leucine incorporation (P<0.01, respectively), while the higher concentrations of SNP (50~500 μmol/L) exerted an inhibitory effect on [3H]thymidine and [14C]leucine incorporation ( P<0. 01. respectively). ODQ ( l-H- [1,2,4]oxadiazolo[4,3-a]quinoxalin- I-one) could prevent the stimulatory effect of low dose SNP induced [3H]thymidine and [14C]leucine incorporation (P<0. 01, respectively) rather than the inhibitory effecr induced by high dose of SNP. CONCLUSION: NO might exert biphasic effects on cell proliferation and protein syn thesis to the kidney, and its stimulatory effect may be mediated by cGMP.
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