一氧化氮合酶抑制剂对宫内窘迫胎鼠脑组织线粒体结构及功能的影响  

Effects of nitric oxide synthase inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress

作　　者：张华[1] 姚珍薇[1] 吴味辛[1] 

机构地区：[1]重庆医科大学附属第一医院妇产科,400016

出　　处：《中华妇产科杂志》2004年第8期543-547,i002,共6页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的探讨不同类型一氧化氮合酶(NOS)抑制剂对宫内窘迫不同时段胎鼠脑组织线粒体结构及功能的影响。方法(1)建立胎鼠宫内窘迫模型。分为急性缺血组(30只)、治疗1组[30只,于缺血前1.5 h孕鼠腹腔内注射左旋硝基精氨酸(L—NNA)4 mg/kg体重]、缺血再灌注组(30只)、治疗2组(30只,缺血前1.5 h孕鼠腹腔内注射L—NNA 4 mg/kg体重,然后于术前即刻腹腔内注射氨基胍500 mg/kg体重)。另选10只孕17d的正常胎鼠作为对照组。(2)电镜观察各组胎鼠脑组织线粒体的比表面积;RT-PCR测定急性缺血组、治疗1组和对照组胎鼠缺血5 min、15 min、30 min的神经型一氧化氮合酶(nNOS)mRNA的表达量[以吸光度(A)值表示];测定缺血再灌注组、治疗2组和对照组胎鼠脑组织诱生型一氧化氮合酶(iNOS)活性和线粒体Na+K+-ATP酶及细胞色素氧化酶的活性。结果(1)急性缺血组缺血5 min、15 min、30 min nNOS A值分别为0.51±0.02、0.76±0.01、0.98±0.02,治疗1组分别为0.29±0.01、0.45±0.03、0.96±0.01。在5 min,15 min两个时间点上,急性缺血组nNOS A值明显高于治疗1组(P<0.05)。且两组nNOS A值均明显高于对照组的0.19±0.02。(2)缺血再灌注组再灌注6 h、12 h、24 h iNOS活性分别为(5.24±0.09)、(7.05±0.22)、(9.33±0.09)U/毫克蛋白(mg·prot),Objective lo evaluate the effects ot different types oi nitric oxide synthase inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress. Methods Rats were divided into control group, acute ischemia group, treatment group 1 injection of [ N omega-nitro-L-arginine (L-NNA) 4 mg/kg into pregnant rats' abdomen before ischemia], reperfusion group, treatment group 2 [injection of L-NNA 4 mg/kg into pregnant rats' abdomen before ischemia followed by injection of aminoguanidine (AG) 500 mg/kg before operation]. Changes of mitochondrial structure were observed by transmission electron microscopy and expression of neuronal nitric oxide synthase (nNOS) mRNA (A) through RT-PCR. Inducible nitric oxide synthase ( iNOS) activity and mitochondrial Na+ K + -ATPase and cytochrome oxidase activity were measured. 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 groups (P >0. 05). But the A of nNOS in two groups was higher than that in control group ( P < 0. 05). (2) iNOS activities in reperfusion group were all higher than those in treatment group 2. Both of those in two groups were higher than that in control group (P < 0. 05). (3) Mitochondrial Rsv (5 min, 15 min) in acute ischemia group was smaller than those of treatment group 1 ( P < 0. 05 ) . There was no difference between mitochondrial Rsv (30 min) in two groups ( P >0. 05 ). Mitochondrial Rsv in reperfusion group was all smaller than those in treatment group 2. And mitochondrial Rsv in all the groups was smaller than that in control group( P < 0. 05) . (4) Na+K+-ATPase activity in treatment group 2 was higher than those in reperfusion group (P <0. 05). Na+ K+ -ATPase activity in two groups was lower than that in control group (P < 0. 05) . Conclusions nNOS and iNOS play a role in cerebral mitochondrial structure and function damage in fetal rats with intrauterine distress. L-NNA has some limited treatm

关 键 词：治疗 胎鼠 线粒体 急性缺血 缺血再灌注 对照组 脑组织 K^+-ATP酶 Na^+ 结构和功能 

分 类 号：R96[医药卫生—药理学]