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中华妇幼临床医学杂志(电子版) ›› 2006, Vol. 02 ›› Issue (04) : 198 -202. doi: 10.3877/cma.j.issn.1673-5250.2006.04.106

论著

胎鼠缺血缺氧性脑损伤时一氧化氮合酶与线粒体介导的神经细胞凋亡的关系及其抑制剂的保护作用
张华, 姚珍薇   
  1. 重庆医科大学附属第一医院妇产科(重庆,400016)
  • 出版日期:2006-07-21

The relationship of nitric oxide synthase and neuron apoptosis mediated by mitochondria in fetal rats hypoxic ischemic encephalopathy and the protective role of NOS inhibitors

Hua ZHANG, Zhen-wei YAO   

  1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University.Chongqing, 400016, China
  • Published:2006-07-21
引用本文:

张华, 姚珍薇. 胎鼠缺血缺氧性脑损伤时一氧化氮合酶与线粒体介导的神经细胞凋亡的关系及其抑制剂的保护作用[J/OL]. 中华妇幼临床医学杂志(电子版), 2006, 02(04): 198-202.

Hua ZHANG, Zhen-wei YAO. The relationship of nitric oxide synthase and neuron apoptosis mediated by mitochondria in fetal rats hypoxic ischemic encephalopathy and the protective role of NOS inhibitors[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2006, 02(04): 198-202.

目的

探讨一氧化氮合酶(nitric oxide synthase,NOS)与线粒体介导凋亡过程中能量代谢、细胞色素C和天冬氨酸特异的半胱氨酸蛋白酶-3(Caspase-3)的相互关系及其抑制剂的保护作用。

方法

①建立胎鼠宫内窘迫模型。②分为5组:对照组、急性缺血组、治疗1组、缺血再灌注组、治疗2组。③检测脑组织中caspase-3的表达、细胞色素C的胞浆释放量;检测胎鼠脑组织神经型一氧化氮合酶(nNOS)mRNA表达量[以吸光度(A)值表示],诱生型一氧化氮合酶(iNOS)、线粒体细胞色素氧化酶活性。分析不同时段细胞色素氧化酶活性、细胞色素C胞浆释放量及caspase-3阳性细胞数的变化趋势。

结果

①急性缺血组在5 min,15 min两个时间点nNOS A值明显高于治疗1组,差异有显著意义(P<0.05),且两组nNOS 4值均明显高于对照组。②缺血再灌注组各时间点iNOS活性明显高于治疗2组(P<0.05),且两组iNOS活性明显高于对照组(P<0.05)。③急性缺血组缺血5 min, 15 min线粒体细胞色素氧化酶活性均高于对照组(P< 0.05)。治疗1组缺血30 min线粒体细胞色素氧化酶活性虽高于急性缺血组,但仍低于对照组(P<0.05)。缺血再灌注组和治疗2组各时间点的细胞色素氧化酶活性均低于对照组,而治疗2组的均高于缺血再灌注组(P<0.05)。④在5min,15min两个时间点,急性缺血组及治疗1组的细胞色素C胞浆释放量和caspase-3免疫阳性细胞计数与对照组比较,差异无显著性。缺血30 min时,治疗1组胞浆中细胞色素C含量及caspase-3免疫阳性细胞计数较急性缺血组虽明显降低,但仍高于对照组(P<0.05)。缺血再灌注组和治疗2组胞浆细胞色素C含量及caspase-3免疫阳性细胞计数均高于对照组。治疗2组各时间点的胞浆细胞色素C含量与caspase-3免疫阳性细胞计数低于缺血再灌注组(P<0.05)。

结论

①nNOS和iNOS介导了宫内窘迫不同阶段的胎鼠脑神经细胞细胞色素氧化酶活性的损害、细胞色素C的胞浆释放及caspase-3表达的增加。②左旋硝基精氨酸(L-NNA)在一定时间内对胎鼠脑急性缺血期线粒体能量代谢障碍和神经细胞凋亡有预防作用。而氨基胍(AG)对胎鼠脑缺血再灌注期的线粒体能量代谢障碍和神经细胞凋亡有良好的保护作用。

Objective

Evaluating the relationship of nitric oxide synthase(NOS)and energy metabolism and cytochrome C and caspase-3 during neuron apoptosis mediated by mitochondria and the protective role of NOS inhibitors.

Methods

① Set up fetal rat intrauterine distress model.②Divide into the control group, acute ischemia group, treatment group 1, reperfusion group, treatment group 2.③Measuring expression of caspase-3 and the content of cytochrome C in cytosol.Measuring expression of neuronal nitric oxide synthase(nNOS)mRNA(A)and the activity of inducible nitric oxide synthase(iNOS)and cytochrome oxidase.The change trends of the activity of cytochrome oxidase and the content of cytochrome C and the positive cell number of caspase-3 during different times were analysed.

Results

① The A of NOS(5 min, 15 min)in acute ischemia group was higher than that of treatment group 1(P< 0.05).There was no difference between the A of nNOS(30 min)in two group(P>0.05).But the A of nNOS in two groups was higher than that in the control group(P < 0.05).② iNOS activities in the reperfusion group were all higher than those in the treatment group 2.Both of those in two groups were higher than that in control group(P<0.05).③The activity of mitochondria cytochrome oxidase in the acute ischemia group(5 min, 15 min)were higher than those in the control group(P<0.05).The activity of mitochondria cytochrome oxidase in the acute ischemia group(30 min)was lower than that in the control group(P<0.05).The activity of mitochondria cytochrome oxidase in the treatment groupl(30 min)was higher than that in the acute ischemia group, but lower than that in the control group(P<0.05).The activity of mitochondria cytochrome oxidase in the reperfusion group(6 h, 12 h, 24 h)and the treatment group 2(6 h, 12 h, 24 h)were lower than those in the control group(P < 0.05).The activity of mitochondria cytochrome oxidase in the treatment group 2(6 h, 12 h,24 h)were higher than those in the reperfusion group(P<0.05).④There were no differences between the content of cytochrome C and the positive cell number of caspase-3 in the acute ischemia group(5 min, 15 min)and those in the treatment groupl(P>0.05).The content of cytochrome C and the positive cell number of caspase-3 in the treatment group 1(30 min)were lower than those in the acute ischemia group, but higher than those in the control group(P < 0.05).The content of cytochrome C and the positive cell number of caspase-3 in the reperfusion group(6 h, 12 h,24 h)and the treatment group 2(6 h, 12 h,24 h)were higher than those in the control group(P<0.05).The content of cytochrome C and the positive cell number of caspase-3 in the treatment group 2(6 h, 12 h,24 h)were lower than those in the reperfusion group(P<0.05).

Conclusion

① nNOS and iNOS mediated the damage of cytochrome oxidase's activity and cytochrome C releasing to cytosol and the increase of the expression of caspase-3 during different times of intrauterine distress.② L-NNA play a preventive role in mitochondria energy metabolism failure and neuron apoptosis during acute ischemia stage when intrauterine distress, but effect is limited.AG play a obvious protective role in mitochondria energy metabolism failure and neuron apoptosis when reperfusion following ischemia.

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