一氧化氮合酶在缺血预处理对大鼠肾脏缺血-再灌注损伤保护中的作用

目的：探讨一氧化氮合酶（ＮＯＳ）在缺血预处理对大鼠肾脏缺血－再灌注损伤保护中的作用。方法：将大鼠随机分为对照组（ＣＯＮ）、缺血－再灌注组（ＩＲ）和血预处理后血－再灌注组（ＩＰＣ）。光镜下观察并行肾小管评分,用免疫组化法检测各组中不同灌注时间的３种ＮＯＳ的变化。结果：不同缺血－再灌注时间点病理组织学肾小管评分ＩＰＣ组均低于ＩＲ组,而ＩＰＣ组和ＣＯＮ组之间无显著性差异;诱导型ＮＯＳ在ＩＲ组中的表达明显     

Endothelial nitric oxide contributes to the renal protective effects of ischemic preconditioning

We determined whether endothelial nitric oxide synthase (eNOS) plays an important role in the renal protective effect of ischemic preconditioning (IP) against the ischemia/reperfusion-induced acute renal failure (ARF) by using eNOS-deficient (eNOS(-/-)) and wild-type (eNOS(+/+)) mice. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. IP, which consists of three cycles of 2-min ischemia followed by 5-min reperfusion, was performed prior to 45-min ischemia. In eNOS(+/+) mice, IP treatment markedly attenuated the ischemia/reperfusion-induced renal dysfunction and significantly improved histological renal damage such as tubular necrosis, proteinaceous casts in tubuli, and medullary congestion. Constitutive nitric oxide synthase activity in the kidney without IP was markedly decreased 6 h after reperfusion, but this decreased response was not observed in eNOS(+/+) mice with IP treatment. The improvement of renal dysfunction in eNOS(+/+) mice with IP treatment was abolished by pretreatment with N(G)-nitro-l-arginine, a nonselective NOS inhibitor, whereas aminoguanidine, an inducible NOS inhibitor, had no effect. Finally, no protective effects of IP on ischemia/reperfusion-induced renal dysfunction and histological damage were observed in eNOS(-/-) mice. These findings strongly support the view that eNOS-mediated NO production plays a pivotal role in the protective effect of IP on ischemia/reperfusion-induced ARF.     

一氧化氮合酶在缺血预适应诱导第二心肌保护窗口中的作用

目的探讨一氧化氮合酶在缺血预适应诱导第二心肌保护窗口减少心肌梗死范围中的作用.方法结扎冠状动脉复制心肌缺血预适应及心肌梗死模型.斑点印迹法测定心肌热休克蛋白72含量.结果缺血预适应前静注一氧化氮合酶抑制剂(左旋硝基精氨酸)可使缺血预适应组的心肌梗死范围由(22.6±5.9)%扩大至(40.1±8.3)%,与对照组(44.2±8.1)%水平相似.亦可使缺血预适应诱导的心肌热休克蛋白72表达由3.3±0.8降至2.3±0.8,与对照组水平1.8±0.6相似.结论一氧化氮合酶在缺血预适应诱导第二心肌保护窗口过程中发挥重要作用.其作用可能与其参与诱导心肌热休克蛋白72表达有关.     

血清诱导型一氧化氮合酶和超敏C-反应蛋白与缺血预处理的相关性研究

目的 通过观察梗死前心绞痛对急性心肌梗死(AMI)患者血清诱导型一氧化氮合酶(iNOS)和超敏C-反应蛋白(hs-CRP)水平的影响,探讨缺血预处理(IP)与血清iNOS与hs-CRP的相关性.方法 52例AMI患者于冠状动脉成形术或静脉溶栓前检测血清iNOS活力及hs-CRP水平.根据AMI发作前48 h内有无典型心绞痛发作,将病例分为梗死前心绞痛组[IP(+)组]和非梗死前心绞痛组[IP(-)组].比较两组间血清iNOS活力及hs-CRP水平.结果 IP(+)组血清iNOS活力明显高于IP(-)组(P<0.01).IP(+)组血清hs-CRP水平明显低于IP(-)组(P＜0.05).结论 IP可使血清iNOS活力上调,上调iNOS水平是延迟IP心脏保护作用的机制之一.存在IP者hs-CRP水平较低,冠状动脉炎症反应较轻,抑制炎症反应可能也是IP保护作用的机制之一.     

人参皂甙Rgl对脑缺血后神经元型一氧化氮合酶的影响

目的：观察人参皂甙Rgl对大鼠海马神经元缺糖氧／复糖氧后钙内流和神经元型一氧化氮合酶（nNOS）的影响,并探讨其可能的脑保护机制。方法：建立大鼠海马神经元缺糖氧／复糖氧模型,随机分为正常对照组、模型组和人参皂甙Rgl干预组（5、20、60μmol／L）。复糖氧后24h以Fluo-3AM荧光染色法观察各组海马神经元细胞内钙离子浓度变化,以生物化学法观察nNOS活性的变化,并以Hochest染色法检测细胞凋亡。结果：与模型组相比,人参皂甙Rgl中、高剂量组海马神经元细胞内钙离子浓度和nNOS活性均降低,凋亡细胞减少,人参皂甙Rgl低剂量组变化不明显。结论：人参皂甙Rgl可通过减少缺糖氧神经元细胞内钙内流,进而抑制nNOS活性,发挥脑保护作用。     

Contribution of nitric oxide to the protective effects of ischemic preconditioning in ischemia-reperfused rat kidneys.

We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-reperfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval. I/R treatment consisted of a 30-minute ischemia and 60-minute reperfusion interval. We measured the glomerular filtration rate (GFR), the fractional excretion of sodium (FE(Na)), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, N(G)-nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FE(Na) as compared with I/R treatment; however, this effect was completely abolished by L-NAME injection and enhanced by L-arginine treatment. L-NAME treatment significantly diminished RBF but did not alter nitrite/nitrate excretion. Furthermore, we found that IP alone does not lead to inducible NO synthase protein expression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-1 expression in IP+I/R kidneys as compared with I/R treated ones. Our results clearly showed that IP pretreatment protects kidneys from I/R mediated tissue injury and that these effects were partially mediated by NO.     

Cardioprotection by remote ischemic preconditioning exhibits a signaling pattern different from local ischemic preconditioning

Remote ischemic preconditioning (RIPC) and local ischemic preconditioning (IPC) protect the myocardium from subsequent ischemia/reperfusion (I/R) injury. In this study, the protective effects of early RIPC, IPC, and the combination of both (RIPC-IPC) were characterized. Furthermore, the hypothesis was tested that protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs), important mediators of IPC, are activated in RIPC. Infarct size, serum troponin T, and creatine kinase levels were assessed after 4 × 5-min noninvasive RIPC, local IPC, or a combination of both and 35 min of regional ischemia and 120 min of reperfusion. Protein kinase C ε and the MAPKs extracellular signal-regulated MAPK (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK were analyzed by Western blot analysis and activity assays in the myocardium and skeletal muscle immediately after the preconditioning protocol. Remote ischemic preconditioning, IPC, and RIPC-IPC significantly reduced myocardial infarct size (RIPC-I/R: 54% ± 15%; IPC-I/R: 33% ± 15%; RIPC-IPC-I/R: 33% ± 15%; P < 0.05 vs. I/R [76% ± 14%]) and troponin T release (RIPC-I/R: 15.4 ± 6.4 ng/mL; IPC-I/R: 10.9 ± 7.0 ng/mL; RIPC-IPC-I/R: 9.8 ± 5.6 ng/mL; P < 0.05 vs. I/R [27.1 ± 12.0 ng/mL]) after myocardial I/R. Ischemic preconditioning led to an activation of PKCε and ERK 1/2, whereas RIPC did not lead to a translocation of PKCε to the mitochondria or phosphorylation of the MAPKs ERK 1/2, JNK 1/2, and p38 MAPK. Remote ischemic preconditioning did not induce translocation of PKCε to the mitochondria or phosphorylation of MAPKs in the preconditioned muscle tissue. Remote ischemic preconditioning, IPC, and RIPC-IPC exert early protection against myocardial I/R injury. Remote ischemic preconditioning and local IPC exhibit different activation dynamics of signal transducers in the myocardium. The studied PKC-MAPK pathway is likely not involved in the protective effects of RIPC.     

脑缺血预处理诱导大鼠脑缺血耐受的研究

目的：探讨局灶性脑缺血预处理在大鼠脑缺血耐受巾的作用及机制。方法：线栓法制作大鼠右大脑中动脉阻塞的局灶性脑缺血模型。在缺血预处理组脑缺血预处理15min：3d后，再次阻塞右大脑中动脉8h。评估神经功能缺失、脑梗死体积和右脑组织形态学．免疫组化法检测右脑组织肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）的表达。结果：缺血预处理组大鼠神经功能缺失评分明显改善（P〈0.01）．脑梗死体积明显减小（P〈0.01），缺血损伤改变明显减轻，TNF-α和iNOS的表达也明显减少（P〈0.05）。结论：局灶性脑缺血预处理可诱导大鼠脑缺血耐受，其机制可能是抑制缺血脑组织表达TNF-α及iNOS而减轻炎症免疫损伤。     

捕食应激对大鼠海马一氧化氮及神经型一氧化氮合酶的影响

目的探讨一氧化氮(NO)在创伤后应激障碍(PTSD)样行为异常大鼠的变化规律,以进一步揭示PTSD的神经生物学机制。方法将144只Wistar大鼠随机分组为捕食应激组(n=72)及正常对照组(n=72),在大鼠捕食应激PTSD动物模型基础上,动态检测大鼠海马、额叶皮层组织匀浆NO、一氧化氮合酶(NOS)含量及神经元型NOS(nNOS)表达。结果应激大鼠海马NO含量于捕食应激后即刻明显高于对照组犤(2.8±0.8)μmol/g,F=23.112,P=0.000犦,12h达高峰(3.9±1.1)μmol/g,与对照组比较,F=56.616,P=0.000;与同组其他时相比较,F=14.917,P<0.05,24h时仍明显增多犤(2.6±0.7)μmol/g,F=23.094,P=0.000犦;海马nNOS表达亦同步增高(应激后即刻,12及24h,F=14.228,21.772,18.500,P<0.01),而海马总NOS活性仅在应激后12h内增高犤应激后即刻及12hNOS分别为(9.8±2.5)mmol/(s·kg),F=32.812,P=0.000及(10.2±2.7)mmol/(s·kg),F=31.395,P=0.000犦。结论严重心理/生理应激所致海马nNOS持续性高表达与NO释放明显增多,在实验大鼠持续性PTSD样行为异常中可能有重要作用。     

缺血预处理在肢体再灌注损伤中的保护作用及一氧化氮、内皮素1的变化

目的分析无创性肢体缺血预处理(IPC)对肢体缺血再灌注损伤的干预效果以及NO和ET-1的变化。方法30只大鼠随机均分为对照组和实验组,对照组未经过缺血预处理,直接止血2、3、4 h;实验组经过缺血预处理后,于第2天分别止血2、3、4 h。依次于恢复肢体血流(再灌注)后1、3、7、14 d时抽取血液检测ET-1、NO的水平。结果大鼠体内NO和ET-1在第1、3、7、14天内呈先递增后递减的趋势,实验组NO在第3天缺血4 h时达最大值,对照组NO在第7天缺血2 h时达高峰;实验组ET-1在第7天缺血3h时达最大值,对照组ET-1在第3天4 h时达最大值,差异均有统计学意义(P0.05)。实验组NO在大鼠血液中第1、3、7天的含量在缺血2 h和3 h时均显著低于对照组(P0.01);第14天时,仅缺血2 h时显著低于对照组(P0.01);实验组ET-1在大鼠血液中第1、3、7天的含量在缺血各时间段时均显著低于对照组(P0.01);第14天时,仅缺血3 h时显著低于对照组(P0.01)。结论缺血预处理改变了缺血再灌注损伤后血清NO与ET-1的水平。     

Hypercholesterolemia abrogates sevoflurane-induced delayed preconditioning against myocardial infarct in rats by alteration of nitric oxide synthase signaling

The aim of the current study was to determine whether hypercholesterolemia affects the delayed sevoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury and, if so, the underlying mechanism. Male Sprague-Dawley rats fed 2% cholesterol-enriched chow for 8 weeks were subjected to sevoflurane preconditioning (2.4% vol/vol, 1 h) 24 h before myocardial ischemia was induced by occluding the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The hemodynamic parameters left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rise/fall rate of left ventricular pressure were continuously monitored, and myocardial infarct size was determined at the end of reperfusion. The protein expression of myocardial nitric oxide synthase (NOS), Bcl-2, and Bad was assessed before ischemia. We found that the left ventricular hemodynamic parameters during the whole IR procedure and the myocardial infarct size did not significantly differ between the normocholesterolemic and hypercholesterolemic control groups. The hemodynamic parameters were all markedly improved during the reperfusion period, and the myocardial infarct size was significantly reduced by delayed sevoflurane preconditioning in normocholesterolemic rats, but all of these improvements were reversed by N-(3-(aminomethyl)benzyl) acetamidine (1400W, 1 mg/kg; i.v., 10 min before ischemia), a selective inducible NOS (iNOS) inhibitor, and 5-hydroxy decanoate sodium (5 mg/kg, i.v., 10 min before ischemia), a mitochondrial ATP-dependent K? channel blocker. Such cardiac improvement induced by delayed sevoflurane preconditioning did not occur in hypercholesterolemic rats and was not exacerbated by 1400W or 5-hydroxy decanoate sodium. The expression of myocardial iNOS was markedly enhanced by delayed sevoflurane preconditioning in normocholesterolemic, but not in hypercholesterolemic rats. The expression of endothelial NOS and Bad did not differ among all groups. The expression of myocardial phosphorylated endothelial NOS, Bcl-2, and phosphorylated Bad in normocholesterolemic rats was not affected by delayed sevoflurane preconditioning but was decreased in the hypercholesterolemic control group, and this was not reversed by sevoflurane, compared with the normocholesterolemic control group. Taken together, these results indicate that sevoflurane preconditioning exerts delayed cardioprotection against IR injury in normocholesterolemic rats, which is blocked by hypercholesterolemia potentially via interference with the iNOS/mitochondrial ATP-dependent K? channel pathway.     

缺血预处理及乐脉颗粒对增强局灶性脑缺血耐受的作用机制

目的：观察局灶性的脑缺血预处理对胶质纤维酸性蛋白和神经元特异性烯醇化酶表达的影响，以及给予乐脉颗粒干预治疗后的变化。方法：实验于2003-12／2004-11在四川大学华西医院外科和眼科实验室进行。取SD大鼠30只，随机分为3组，每组10只。①预缺血组：二次线栓法建立脑缺血耐受模型，预缺血10min，3d后给予大脑中动脉完全阻塞2h，再灌注22h。②假手术组：未进行缺血预处理，而单纯暴露动脉处的解剖结构10min，余同预缺血组。⑧乐脉颗粒组：预缺血10min，给予乐脉颗粒（丹参，川芎，赤芍，红花，香附，木香等组成）1．5g／（kg&;#183;d）灌胃，3d后给予大脑中动脉完全阻塞塞2h，再灌注22h。各组大鼠处死前进行神经功能缺损评分（04分，0分为无神经功能缺失症状；4分为不能自发行走）；在再灌注22h麻醉状态下处死大鼠，测定脑梗死体积；进行免疫组化染色和图像分析比较各组纤维酸性蛋白、神经元特异性烯醇化酶的表达，以评估脑组织中星形胶质细胞活化和正常神经元存活情况。结果：30只大鼠进入结果分析。①脑梗死体积：乐脉颗粒组明显小于假手术组与预缺血组[（96．84&;#177;4．99），（147．62&;#177;4．70），（114．33&;#177;7．81）mm^3，P〈0．01]。②神经功能缺损评分：乐脉颗粒组显著低于预缺血组（2．06&;#177;0．08，2．18&;#177;0．22，P〈0．01），两组均低于假手术组（3．18&;#177;0．16，P〈0．01）。⑧胶质纤维酸性蛋白阳性表达的IA值：预缺血组与乐脉颗粒组均高于假手术组（6610．83&;#177;741．43，11937．70&;#177;868．34，3500．53&;#177;143．34，P〈0．05，0．01），但乐脉颗粒组增高更为明显。④神经元特异性烯醇化酶阳性表达的IA值：乐脉颗粒组高于预缺血组和假手术组（9773．58&;#177;614．77，5459．82&;#177;605．14，2666．12&;#177;359．72，P〈0．01）；预缺血组高于假手术组（P〈0．01）。结论：①局灶性缺血预处理10min能够对3d后的SD大鼠脑再梗死提供脑保护，诱导缺血耐受的形成。②局灶性缺血预处理能够诱导缺血耐受的产生，其可能的机制之一是通过促进星形胶质细胞活化增加减少神经元的损伤，乐脉颗粒能够增强这一效应。     

缺血预处理及乐脉颗粒对增强局灶性脑缺血耐受的作用机制

目的:观察局灶性的脑缺血预处理对胶质纤维酸性蛋白和神经元特异性烯醇化酶表达的影响,以及给予乐脉颗粒干预治疗后的变化。方法:实验于2003-12/2004-11在四川大学华西医院外科和眼科实验室进行。取SD大鼠30只,随机分为3组,每组10只。①预缺血组:二次线栓法建立脑缺血耐受模型,预缺血10min,3d后给予大脑中动脉完全阻塞2h,再灌注22h。②假手术组:未进行缺血预处理,而单纯暴露动脉处的解剖结构10min,余同预缺血组。③乐脉颗粒组:预缺血10min,给予乐脉颗粒(丹参,川芎,赤芍,红花,香附,木香等组成)1.5g/(kg·d)灌胃,3d后给予大脑中动脉完全阻塞塞2h,再灌注22h。各组大鼠处死前进行神经功能缺损评分(0～4分,0分为无神经功能缺失症状;4分为不能自发行走);在再灌注22h麻醉状态下处死大鼠,测定脑梗死体积;进行免疫组化染色和图像分析比较各组纤维酸性蛋白、神经元特异性烯醇化酶的表达,以评估脑组织中星形胶质细胞活化和正常神经元存活情况。结果:30只大鼠进入结果分析。①脑梗死体积:乐脉颗粒组明显小于假手术组与预缺血组[(96.84±4.99),(147.62±4.70),(114.33±7.81)mm3,P<0.01]。②神经功能缺损评分:乐脉颗粒组显著低于预缺血组(2.06±0.08,2.18±0.22,P<0.01),两组均低于假手术组(3.18±0.16,P<0.01)。③胶质纤维酸性蛋白阳性表达的IA值:预缺血组与乐脉颗粒组均高于假手术组(6610.83±741.43,11937.70±868.34,3500.53±143.34,P<0.05,0.01),但乐脉颗粒组增高更为明显。④神经元特异性烯醇化酶阳性表达的IA值:乐脉颗粒组高于预缺血组和假手术组(9773.58±614.77,5459.82±605.14,2666.12±359.72,P<0.01);预缺血组高于假手术组(P<0.01)。结论:①局灶性缺血预处理10min能够对3d后的SD大鼠脑再梗死提供脑保护,诱导缺血耐受的形成。②局灶性缺血预处理能够诱导缺血耐受的产生,其可能的机制之一是通过促进星形胶质细胞活化增加减少神经元的损伤,乐脉颗粒能够增强这一效应。     

应用缺氧预处理建立大鼠缺血耐受模型及其特征

背景:应用大鼠脑缺氧耐受实验可以认识内源性神经保护机制.目的:观察脑缺氧预处理大鼠模型的脑缺氧耐受特点.设计:随机对照动物实验.单位:吉林大学中日联谊医院神经内科.材料:实验于2003-04/2004-04在吉林大学中日联谊医院基础动物实验中心完成.纯系健康Wistar大鼠,随机分为正常对照组、假手术组, 6只/组;缺血对照组,20只,预缺氧(3 h,8%O2和92%N2) 缺血组:60只,根据缺氧时间不同分为5个时相点,即30 min,1,3,5,6 h点,每个时相点12只大鼠.预缺氧组:18只,根据缺氧时间不同分为3个时相点,即1,3,5 h点,每个时相点6只大鼠(3只用于TTC染色,3只用于苏木精-伊红).方法:①缺氧预处理:在固定体积的密闭玻璃容器中,首先放入钠石灰吸收二氧化碳和氧气,然后输入8%O2和92%N2的混和气体,放入动物,3只/次.并尽量保持温度、湿度恒定.②建立大鼠大脑中动脉永久性缺血模型.③通过神经病学评分、梗死体积判定、病理标本制作、免疫组织化学染色、图像分析等一系列步骤对该模型进行评价.④组间比较采用方差分析.主要观察指标:实验组和对照组大鼠脑梗死体积、神经病学评分及病理形态学改变.结果:预缺氧(8%O2,1,3,5 h) 缺血组神经功能评分,低于缺血对照组 (P＜0.01).缺氧8% O2,30 min及6 h)组神经功能评分,与缺血对照组相比差异无显著性(P＞0.05).预缺氧(8%O2,1,3,5 h) 缺血组脑梗死平均体积比,低于缺血对照组,(P＜0.01).缺氧 (8% O2,30 min及6 h)组平均梗死体积比为与缺血对照组相比差异无显著性 (P＞0.05).结论:大鼠缺氧预处理,能有效减轻局灶性脑缺血所致的神经损伤,具有脑保护作用.用缺氧预处理建立的脑缺血耐受模型操作简便,稳定性好,对实验动物损伤小,是一种研究脑缺血耐受的有用工具.     

The role of nitric oxide and prostaglandin signaling pathways in spinal nociceptive processing in chronic inflammation

Both nitric oxide (NO) and prostaglandins (PG) and their associated enzymes nitric oxide synthases (NOS) and cyclooxygenases (COX) (specifically COX-2) have been implicated in the development of hyperalgesia. This study examined the effects of naturally occurring chronic inflammation, chronic mastitis, on spinal nociceptive processing in sheep and focused on potential alterations in spinal PG and NO signaling pathways. Mechanical withdrawal thresholds were significantly lower in animals suffering from chronic inflammation (n=6) compared to control animals (n=6). Hyperalgesia was restricted to the side contralateral to the inflammation (decrease from ipsilateral side: hindlimb 33.2+/-5%, forelimb 19.4+/-5%). Neuronal NOS-immunoreactivity was significantly reduced bilaterally in lumbar and cervical spinal cord throughout laminae I-III (decrease 18.4+/-5% and 16.9+/-4%, respectively) and in lamina X (decrease 29.1+/-6% and 17.1+/-4%, respectively) in mastitic animals relative to control animals. No difference was detected in eNOS or iNOS-immunoreactivity or in NADPH-diaphorase staining, a marker of dynamically active NOS. RT-PCR failed to detect any change in levels of nNOS, eNOS, iNOS, COX-1 or COX-2 mRNAs. However, a marked increase in the PGE receptor, EP(3) (but not EP(2)) mRNA was detected in ipsilateral spinal cord tissue from animals with chronic inflammation. This increase in EP(3) receptor expression indicates that spinal PGs are important in the spinal response to chronic peripheral inflammation. Contralateral mechanical hyperalgesia may not be directly linked to changes in spinal EP(3) receptor mRNA expression, however, the bilateral changes in nNOS suggest that this pathway may contribute to the adaptive behavioural response observed.     

小剂量一氧化氮合酶抑制剂对局灶性脑缺血神经细胞损伤的影响

背景:一氧化氮在神经系统中的作用是近10年来的研究热点之一,而其在脑缺血过程中对神经细胞的损伤的何保护性作用?目的:研究一氧化氮在局灶性脑缺血再灌流过程中对病理改变的影响,并探讨其机制。设计:完全随机对照开放实验。地点和对象:实验地点:吉林大学第一医院神经科研究室;研究对象:Wistar大鼠70只,雌雄各半,体质量200～250g,由本校实验动物部提供。干预:利用N-硝基-左旋-精氨酸(N-nitro-L-arginine,NNLA)干预局灶性大鼠脑缺血模型。主要观察指标:通过光、电镜及未端脱氧核糖核酸介导生物素化脱氧尿嘧啶缺口未端标记(terminaldeoxyribonucleotidetransferase-mediateddUTP-biotinnickend-labeling,TUNEL)法观察局灶脑缺血大鼠脑组织的病理学改变。结果:缺血再灌1d时光镜下皮质、海马区均可见神经细胞呈坏死样改变;电镜下半影区神经细胞的改变仅见于核染色质凝集(类似凋亡小体)和小胶质细胞核变形,以细胞凋亡为主;小剂量给予NNLA干预后坏死和凋亡的病理改变均较手术对照组轻(P<0.01)。TUNEL显示与病理改变结果一致(P<0.01)。结论:局灶性脑缺血后,调节一氧化氮生成量在适当范围,可以保护、防止神经细胞进一步损伤。