褪黑素在大鼠慢性肾功能衰竭进展中对肾组织细胞增殖和凋亡的影响

The effect and significance of melatonin on proliferation and apoptosis in rats during the process of chronic renal failure

目的:研究褪黑素(MEL)在大鼠慢性肾功能衰竭进展中对肾组织细胞增殖、凋亡的影响和意义。方法:150只SD大鼠,随机分为3组:CTL组(假手术组)、STN组(5/6肾切除组)、MEL组(5/6肾切除+MEL使用组)。MEL使用40周,分别于1周、2周、8周、12周、16周和40周共6个不同的时间点采用免疫组化和TUNEL法检测增殖细胞核抗原(PCNA)表达与肾组织细胞凋亡的情况。结果:STN组:肾小球系膜区、肾小管术后2～12周内增殖指数较CTL组显著升高(P<0.05),术后16～40周内凋亡指数较CTL组显著升高(P<0.05),术后2～8周内增殖/凋亡比值较CTL组显著升高(P<0.05);肾间质在术后增殖指数持续升高,与CTL组比较,差异显著(P<0.05),其凋亡不明显,增殖/凋亡比值在术后16周内较CTL组显著升高(P<0.05)。MEL组:肾小球系膜区、肾小管术后16～40周内凋亡指数较STN组显著下降(P<0.05),术后16～40周内增殖/凋亡比值较STN组显著升高(P<0.05);肾间质8周前增殖指数、增殖/凋亡比值较STN组显著下降(P<0.05),术后4～8周内凋亡指数较STN组显著升高(P<0.05)。结论:褪黑素能够平衡肾小球系膜区、肾小管上皮细胞、肾间质细胞的增殖与凋亡,保护肾功能。

Aim： To study the effeets of long-term administration of melatonin on proliferation and apoptosis in rats during the process of chronic renal failure. Methods：lSO SI） rats were derided into three groups randomly. The abdominal cavity of control（CTL） group was opened and closed after renal envelope had been peeled off. The kidney of subtotal nephrectomy （STN）group was suhjected to 5/6 subtotal nephrectomy by a two-step produre. The rat of mclatonin（MEL） was given melatonin to STN rats. By taken melatonin for 40 weeks,the changes of proliferating cell nucler antigen（ PCNA）, apoptotic ceils by immunohistochemical labeling and terminal deoxynueleotidyl transferase mediated dUTP nick end labeling （TUNEL） at 1st, 2nd,8th, 12th, 16th and 40th week after operation have been observed. Results：STN group： The proliferation indexes of glo- merulus and tubules cells were higher than those in CTL group after operation within 2 - 12 weeks（P 〈 0.05）. The apoptosis indexes of glomcrulus and tnbules cells were higher than those in CTL group after operation within 16 - 40 weeks（ P 〈 0.05 ）. The proliferation and apoptosis rate of glomerulus and tubules cells were higher than those in CTL group after operation within 2 -8 weeks（P 〈0.05）. The interstitial cells sustained at a higher level which had statistic difference compared with CTL group（ P 〈 0. 05）. Although the apoptosis index of interstitial cells was not significant, The proliferation and apoptosis rate of interstitial cells was higher than those in CTI, group after operation within 16 weeks（P 〈0.05 ）. MEI. group： The apoptosis indexes of glomerulus and tubules cells were lower than those in STN group after operation within 16 - 40 weeks（ P 〈 0.05）. The proliferation anti apoptosis rates of glomerulus and tubules cells were higher than thuse in STN group after operation within 16 - 40 weeks（ P 〈0.05）. The proliferatiun indexes, the proliferation and apoptosis rate of interstitial cells were lessened remarkahly compared with STN group before 8 weeks（ P 〈 0.05）. The apoptosis indexes of interstitial cells were higher than those in STN group after operation within 4 -8 weeks（ P 〈 0.05 ）. Gonclusion： Melatonin can balance the proliferation and apoptosis of glomerulus ,tubules and interstitial ceils. Melatonin can improve the renal function and protect pathological morphology.