自发性高血压大鼠脑缺血后脑区一氧化氮的变化

目的：研究自发性高血压大鼠（SHR）脑缺血后大脑皮质、海马、纹状体和小脑组织中一氧化氮（NO）的变化。采用放射免疫法和荧光分光光度法检测脑组织中一氧化氮合酶（NOS）和亚硝酸盐（NO2）的含量。结果显示SHR脑缺血10min,各脑区NOS和NO2,的含量均明显高于假手术组（P<0．01或P＜005）。说明了SHR脑缺血早期脑组织NO的生成增加．提示用特异的NO生成抑制剂类药物,可能有助于脑缺血的治疗。     

大鼠脑冷冻伤后脑组织NOS活性的变化

目的研究大鼠脑组织冷冻伤后一氧化氮合酶（ＮＯＳ）活性的变化规律。方法利用液氮杯硬膜外冷冻大鼠顶叶脑组织复制冷冻伤模型，测定大鼠脑冷冻伤后不同时间脑组织ＮＯＳ活性。结果大鼠冷冻伤后３０ｍｉｎ局部脑组织ＮＯＳ活性增加（Ｐ＜０．０５），６０ｍｉｎ达较高水平（Ｐ＜０．０１），２ｈ有所下降（Ｐ＜０．０５），６ｈ左右再次升高，直至１２ｈ仍维持高水平（Ｐ＜０．０１）。结论表明大鼠脑组织冷冻伤后ＮＯＳ活性增高，ＮＯ是导致大鼠冷冻伤脑水肿的一重要因子     

亚低温对大鼠短暂性全脑缺血后皮质NOS亚型表达及神经元凋亡的影响

目的观察亚低温对大鼠全脑缺血再灌注后皮质3种一氧化氮合酶亚型表达、一氧化氮产生以及神经元凋亡的影响,探讨亚低温的神经保护机制。方法成年雄性SD大鼠,采用双侧颈总动脉阻断闭塞+低血压法制备短暂性全脑缺血动物模型,随机分为常温缺血组、亚低温缺血组和常温假手术对照组;常温时的脑温为36.5℃～37.5℃,肛温为35.9℃～36.9℃;亚低温时控制在32.5℃～33.5℃,相对应肛温为32.2℃～33.1℃;分别于缺血后及亚低温治疗后30min、2h、24h和72h观察短暂缺血对脑组织一氧化氮合酶亚型表达及神经元凋亡的影响,以及亚低温对缺血性脑损伤的保护作用。行神经元尼氏体亚甲蓝染色观察神经元数目及形态学的变化;免疫组化染色检测神经元型、诱导型和内皮型一氧化氮合酶的表达水平;应用硝酸还原酶法检测硝酸盐/亚硝酸盐水平的变化;采用TUNEL染色法并结合电子显微镜观察神经元凋亡的变化。结果常温缺血组大鼠额叶皮质3种一氧化氮合酶亚型表达水平及硝酸盐/亚硝酸盐含量均明显高于常温假手术对照组(P<0.05或P<0.01),出现凋亡神经元;低温缺血组大鼠3种一氧化氮合酶亚型表达水平和硝酸盐/亚硝酸盐含量明显低于常温缺血组(P<0.05或P<0.01),未检测到凋亡神经元。结论脑缺血后一氧化氮参与了神经元的凋亡过程,而亚低温治疗可以     

大鼠急性局灶性脑缺血再灌注脑组织NO含量和NOS活性的变化

目的探讨一氧化氮（ＮＯ）和神经元型ＮＯ合酶（ｎＮＯＳ）是否参与急性局灶性脑缺血再灌注的发病机理。方法采用栓红法建立大鼠大脑中动脉阻塞（ＭＣＡＯ）模型,观察脑组织ＮＯ含量和一氧化氮合酶（ＮＯＳ）活性的变化及ｎＮＯＳ抑制剂７－硝基吲唑（７－ＮＩ）对再灌注期两者的影响。结果缺血３０分种ＮＯ含量和ＮＯＳ活性显著升高,缺血３小进两者下降;再灌注３０分种ＮＯＴ和ＮＯＳ再次升高,而再灌注３小时两者又下降。７－Ｎ     

西比灵对鼠脑缺血再灌注损伤模型的血清及脑组织中SOD、MDA、N0、NOS含量及病理学的影响

目的 研究西比灵对鼠脑缺血再灌注损伤模型的血清及脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、一氧化氮合酶(NOS)的含量及病理学改变的影响。方法 选用21只沙土鼠并随机分为3组,脑缺血再灌注组(再灌注组)、西比灵预防组(预防组)及对照组,每组7只,分别测定血清、脑组织中SOD、MDA、NO、NOS的含量,并用电镜检测其病理学的变化。结果 与对照组比较,再灌注组显示严重的病理损害,其血清、脑组织中MDA、N0、NOS含量明显上升、SOD含量明显下降,两组比较有显著性差异(均P<0.01);与再灌注组比,预防组病理改变较轻,其血清、脑组织中MDA、NO、NOS明显下降,SOD明显上升,两组比较均有显著性差异(分别P<0.01和P<0.05)。结论 西比灵可减少自由基,诱导SOD生成,具有保护脑细胞的作用。     

高压氧对急性CO中毒大鼠小脑组织NO及NOS活性的影响

目的　研究高压氧(HBO)对急性一氧化碳(CO)中毒大鼠小脑组织中一氧化氮(NO)、一氧化氮合酶(NOS)活性的影响,探讨NO、NOS与急性CO中毒脑损伤的关系及HBO对NO、NOS的作用机制。方法　实验用Wistar大鼠80只,随机分为5组正常对照组(C),CO染毒组(CO),CO染毒+HBO1次治疗组(HBO1),CO染毒+HBO3次治疗组(HBO     

重症肌无力患者IgG对大鼠脑内NOS不同时间表达的影响

目的观察重症肌无力(myasthenia gravis,MG)患者IgG(AchRab)对大鼠脑内一氧化氮合酶(NOS)表达的影响,探讨NOS在MG中造成中枢神经系统损害的机制.方法将AchRab IgG或健康人的IgG注入大鼠侧脑室,1次/d,连续4次.免疫组化方法观察不同时间点大鼠脑皮质、海马及杏仁核神经元型一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)的表达变化.结果侧脑室注射后1周实验组大鼠皮质、海马神经元nNOS表达量明显减少,后2周实验组皮质、海马神经元nNOS表达下降更为明显,同时杏仁核神经元nNOS表达量也减少;实验组及对照组脑内细胞均未见iNOS表达.结论AchRab侧脑室内注射可引起大鼠皮质、海马及杏仁核神经元nNOS表达量减少,且2周内这种减少效应随时间延长而增强,但未能诱导脑内细胞iNOS表达,提示AchRab尚可通过抑制大鼠中枢神经系统nNOS表达,降低脑内正常的一氧化氮浓度,减弱一氧化氮对脑组织的保护作用,增加神经元的易损性.     

曲马多预先给药对切口痛大鼠脊髓NOS活性和NO含量的影响

目的评价曲马多对切口痛大鼠脊髓NOS活性和NO含量的影响,探讨曲马多镇痛效应的机制。方法成年雄性SD大鼠24只,体质量200～250g,随机分为3组,每组6只,对照组(C组)仅给与麻醉及腹腔注射生理盐水5ml,切口痛组(Ⅰ组)于手术前30min腹腔注射生理盐水5ml,曲马多组(T组)于手术前注射曲马多10mg/kg。制备大鼠右后爪切口痛模型,采用累积疼痛评分法评定痛行为学,于术前30min和术后2h测定大鼠机械痛阈和热痛阈,并测定脊髓NOS活性和NO含量。结果与对照组比较,术后2h切口痛组大鼠的累计疼痛评分明显升高(P<0.01),机械痛阈和热痛阈明显降低(P<0.01)。与切口痛组比较,曲马多组术后2h的疼痛累计评分明显降低(P<0.01),机械痛阈和热痛阈明显升高(P<0.01)。与对照组比较,切口痛组NOS活性和NO含量均明显增加(P<0.01)。与切口痛组比较,曲马多组NOS活性,NO含量均明显减少(P<0.01)。结论曲马多10mg/kg腹腔内预先给药,术后疼痛累积评分明显降低,机械痛阈和热痛阈升高,并且能使脊髓NOS活性明显降低,NO含量明显减少。     

70001/经穴输氧对大鼠颅脑损伤后血液流变学、SOD、MDA及NOS含量影响的实验研究

摘　要:目的:探讨经穴输氧治疗大鼠颅脑损伤的作用机制。方法: SD大鼠100只被随机分为正常组、假损伤对照组、电针组(取百会、足三里、阳陵泉、三阴交等穴电针治疗) 、常规治疗组(给予仙台合剂0.417ml /100g) 、经穴输氧组(将氧气按0.01ml /min输入穴位) 5组。后3组大鼠制备脑损伤模型。各组除给予常规治疗外进行对应治疗14天后活杀动物取双侧脑组织,检测脑组织超氧化物岐化酶、丙二醛含量及一氧化氮合酶(NOS) 活性变化并观察各组血液流变学的改变;同时进行脑组织病理观察。结果:各治疗组SOD含量低于正常对照组( P < 0. 05) ,经穴输氧组高于各治疗组( P均< 0. 05) ,经穴输氧组MDA含量高于正常对照组( P < 0. 05) ,而低于各治疗组( P均< 0. 05) ;与假损伤对照组比较, 各治疗组可显著降低伤侧及对侧脑组织NOS 活性, 差异有显著性(P < 0.05 或P < 0.01) ; 且经穴输氧组伤侧NOS 活性显著低于电针组和常规治疗组(P < 0.05 和P < 0.01);大鼠脑损伤后经穴输氧治疗后血液流变学指标发生显著性变化, 全血高切比黏度、高切还原比黏度均显著低于空白对照组, 与电针组比较, 全血高切比黏度、高切还原比黏度、血细胞比容均有显著性差异(P 均< 0.05) , 而纤维蛋白变化不大。治疗前创伤各组双侧半球不对称,伤侧半球明显肿胀,挫伤中心区有出血、神经细胞坏死,挫伤周边神经组织水肿、细胞肿胀、毛细血管塌陷、有血管外出血;治疗后各组均为正常脑表现。结论:经穴输氧对大鼠脑损伤后遗症有效,可以改善脑部血供,改善血液流变性,纠正组织缺血缺氧,使机体具有对抗自由基损害的具有保护神经细胞或促进神经修复,为进一步研究中西结合治疗脑损伤提供思路。     

Mortality and histological findings of the brain during and after cerebral ischemia in male and female spontaneously hypertensive rats

Mortality and pathological changes of the brain during and after cerebral ischemia induced by bilateral carotid artery occlusion (BCO) were studied in male and female spontaneously hypertensive rats (SHR). Systolic arterial blood pressure at rest was significantly higher in male SHR (228 +/- 13 mm Hg, mean +/- S.E.M.) than female (192 +/- 12) (P less than 0.05). The average survival time during permanent occlusion was 11 +/- 6 h (mean +/- S.D.) in male SHR and 17 +/- 7 in female (P less than 0.005), though the cumulative mortality during 24-h ischemia was not different between male (88%) and female SHR (84%). Severe ischemic changes of nerve cells in the brain, especially in the cortex and hippocampus, were observed in 50% of male SHR at 3-h ischemia, while only 15% was observed in female SHR even after 7-h ischemia. After the temporary ischemia followed by reperfusion for 24 h, the mortality was varied between male and female SHR; 0, 31 and 100% after 1-, 3- and 5-h ischemia, respectively, in male SHR and 0% after 1- to 3-h ischemia and 33% after 5- to 7-h ischemia, respectively, in female. Ischemic changes of the brain tissue, such as acidophilic cytoplasm, nuclear degeneration and intercellular edema, were more frequent and severe in male SHR than female after recirculation following 3- or 5-h ischemia. It is concluded that the mortality and post-ischemic viability seem to be determined by the duration of ischemia and also by the degree of the neuronal damage, and female SHR is more tolerated for ischemic insult in comparison to male SHR.     

Regional brain concentrations of vasoactive intestinal polypeptide in normotensive Wistar-Kyoto and spontaneously hypertensive rats

The regional brain and spinal cord concentrations of vasoactive intestinal polypeptide immunoreactivity (VIP) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of VIP in the WKY strain was cortex (44 pmol/g) greater than hippocampus = striatum greater than midbrain = hypothalamus greater than medulla oblongata/pons = lumbar spinal cord (SC) greater than cervical SC greater than thoracic SC (2.5 pmol/g) whereas in the SH strain this order was cortex (35 pmol/g) greater than striatum = midbrain greater than hippocampus = hypothalamus greater than medulla oblongata/pons = lumbar SC greater than cervical SC greater than thoracic SC (1 pmol/g). The VIP concentrations of the thalamus, cerebellum and pituitary were at the level of assay sensitivity (0.5 pmol/g) in both strains. In comparison to the WKY, the SH rats had significantly lower VIP levels in the hippocampus (-42%) and cervical (-46%) and thoracic (-56%) spinal cord but significantly higher levels in the midbrain (+64%).     

A modified citrulline assay of NOS activity in rat brain homogenates does not detect direct effects of halothane on the kinetics of NOS activity

An improved citrulline radioassay of nitric oxide synthase (NOS) activity was developed to study the direct effects of the volatile anesthetic (VA) halothane on the enzyme kinetics of neuronal NOS derived from different regions of the rat central nervous system (CNS). The V_max of NOS in both soluble cytosolic and membrane bound particulate fractions varied across regions with greatest activity in the cerebellum and least in the spinal cord. In contrast, the K_m was not different across regions or in the cytosolic and particulate fractions. Halothane at 0.5, 1, 2 or 3% delivered concentration had no effect on either kinetic parameter of NOS in any of the regions studied indicating that the VAs have no direct effects on NOS activity.     

Cholecystokinin-induced release of dopamine in the nucleus accumbens of the spontaneously hypertensive rat

Changes in dopamine neurotransmission in the nucleus accumbens of the spontaneously hypertensive rat (SHR) may be involved in the pathogenesis of hypertension. This investigation tested the hypothesis that the sulfated octapeptide cholecystokinin (CCK8S) induced release of dopamine is greater in the SHR than in its normotensive control, the Wistar-Kyoto rat (WKY). Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were sampled using microdialysis in the caudal half of the nucleus accumbens of 10-week-old anesthetized SHRs and WKYs. Samples were collected in the following order: 3 baseline, 3 CCK8S (10 μmol/l), and 3 postdrug samples. The samples were then analyzed using high pressure liquid chromatography with electrochemical detection. CCK8S increased dopamine and DOPAC levels in both the SHR and WKY with a larger increase in basal dopamine in the SHR (greater than 200%). Perfusion of the nucleus accumbens with 1 μmol/l of CCK8S or the nonsulfated form of CCK8 (CCK8US, 10 μmol/l) produced no significant increase in the release of dopamine in the SHR. These results indicate that CCK8S-induced release of dopamine in the nucleus accumbens is greater in the SHR. Changes in CCK8S neurotransmission/receptor function may be responsible for the alterations in dopaminergic function of the SHR and the pathogenesis of hypertension.     

SHR在MCAO后脑组织NOS活性的变化

一氧化氮（ＮＯ）在脑缺血中起重要作用，一氧化氮合成酶（ＮＯＳ）作为ＮＯ合成的关键酶，其活性变化直接调节ＮＯ的生成量及生物学效应。本文在建立ＳＨＲＭＣＡＯ局灶脑缺血模型基础上，测定脑缺血后不同时间和正常脑组织的ＮＯＳ活性，结果显示脑缺血早期（１、４ｈ），晚期（２４、４８ｈ）ＮＯＳ活性明显升高，提示脑缺血后缺血组织ＮＯ含量增加。     

The activity of catecholamine synthesis in the hypothalamus of female normotensive Wistar Kyoto and spontaneously hypertensive rats

The activity of catecholamine synthesis in the hypothalamus, as determined by the rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after the administration of a DOPA decarboxylase inhibitor, was compared among Wistar, spontaneously hypertensive (SH), and genetically matched normotensive Wistar Kyoto (WKY) rats. DOPA accumulation in the median eminence, an index of the activity of tuberoinfundibular dopaminergic neurons, was greater in SH rats than Wistar and WKY rats while DOPA accumulation in the medial preoptic area was smaller in Wistar rats than SH and WKY rats. No strain difference was found in DOPA accumulation in the corpus striatum, which represents the activity of nigrostriatal dopaminergic neurons. These results suggest that there are differences in catecholamine synthesis in the hypothalamus not only between SH and WKY rats but also between WKY and Wistar rats.     

Heightened blood pressure and drinking responsiveness to intracerebroventricularly applied angiotensins in the spontaneously hypertensive rat

The effects of bolus intracerebroventricular (i.c.v.) injections of angiotensin II (AII) and angiotensin III (AIII) on blood pressure and water consumption were investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. administered AII and AIII was observed in the SHR as compared with WKY and SD strains for both pressor and drinking responses. The results are consistent with the notion that the SHR has a genetic defect that directly perturbs central angiotensinergic transmission. Two types of defects appear plausible, an alteration in the central angiotensin receptor and its associated transduction system and/or a decrease in the efficiency of signal termination. The present results are interpreted to primarily support the second possibility that a dysfunction in central aminopeptidase activity results in an extended life expectancy of angiotensin, and perhaps other peptides, that contribute to the hypersensitivity seen in the SHR.     

Megakaryocytopoiesis in spontaneously hypertensive rats (SHR)

Bone marrow megakaryocytes and their progenitors were studied in SHR in order to obtain more information about megakaryocytopoiesis in hypertension since it is known that various anomalies of platelet function occur in hypertension. Megakaryocytopoiesis under steady state conditions and following stimulated erythropoiesis and thrombocytopenia was not found to be significantly different in SHR from that in normotensive Wistar controls.     

大鼠实验性脑损伤血浆中NO及NOS的动态变化研究

目的 测定实验性脑损伤后血浆中一氧化氮含量、一氧化氮合酶活性,研究其与脑水肿之间的关系.方法 大鼠随机分组,用硝酸还原酶法测定血清中NO含量、NOS活性,及测定脑组织含水量.并行还原型辅酶Ⅱ依赖性黄递酶(NADPⅡ-d)组化染色检测皮层及脑底NOS阳性细胞.结果 (1)TBI后血浆内NO含量、NOS活力即有升高,与对照组比较有明显差异(P＜0.05).(2)脑组织含水量在外伤后升高,与对照组比较有明显差异(P＜0.05).与血浆中NO含量、NOS活力变化趋势一致.(3) NADPⅡ-d组化染色显示TBI皮层NOS阳性细胞明显多于正常对照组,伤灶脑底也出现了染色块及浓染的细胞群与阳性纤维束.结论 大鼠TBI后NO含量、NOS活性的升高,与脑水肿的发生有关.