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1.
Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities 总被引:2,自引:0,他引:2
Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti-NO and NO-based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO-centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents. 相似文献
2.
《Expert opinion on biological therapy》2013,13(7):867-878
NOS gene therapy has been the focus of extensive research as dysfunction of this enzyme has been implicated in several cardiovascular diseases. Research has concentrated on comparing the effect of gene delivery of NOS isoforms (eNOS, iNOS and nNOS) in healthy and diseased animal models on intimal hyperplasia, restenosis, vascular tone and ischemia-reperfusion injury. Most results demonstrate therapeutic benefits following vascular gene delivery of all NOS in pre-clinical models of cardiovascular disease. eNOS has been shown to have particular promise as it promotes re-endothelialisation and inhibits intimal hyperplasia in injured blood vessels. The ultimate goal is to translate the benefit of NOS gene therapy in animal models into clinical practise. To develop NOS gene therapy for clinical use further work needs to be undertaken to improve delivery systems and vectors to minimise detrimental side-effects and enhance positive treatment outcomes. This review focuses on current research on NOS gene therapy in cardiovascular disease and identifies the next steps that would be necessary to lead to clinical trials. 相似文献
3.
Nitric oxide in vascular biology 总被引:4,自引:0,他引:4
Summary. Nitric oxide is a highly versatile heterodiatomic molecule that effects a variety of actions in the vasculture. Originally identified as a principal determination of vascular tone, nitric oxide has since been recognized to exert anti thrombotic, antiproliferative, and anti-inflammatory effects in the vasculture. At higher concentrations and in the setting of other oxidants, nitric oxide can promote vascular pathology. In this review, we summarize the molecular mechanisms of nitric oxides actions in vascular biology and pathology. 相似文献
4.
Background:
Although inflammation is a normal part of wound healing, if the inflammatory response is excessive the repair process might be prolonged. Nitric oxide (NO) has been implicated in healing inflammation and wounds.Objective:
Endotoxins and cytokines associated with sepsis induce NO synthesis in the tissues. This study used tensile strength and tissue hydroxyproline levels as proxies for wound healing to determine whether wound healing in the presence of endotoxemia is improved when NO synthase is inhibited by N-nitro-l-arginine methyl ester (L-NAME) or N5-(1-Imino-methyl)-l-ornithine (L-NIO).Methods:
In this investigator-blinded, controlled, experimental study, male Wistar albino rats (275-300 g) were divided into 4 groups. The first group received an intraperitoneal (IP) injection of Escherichia coli endotoxin 10 mg/kg and an SC injection of 0.9% sodium cloride (NaCl). The second group received IP E coli 10 mg/kg and SC L-NAME 2 mg/kg. The third group received IP E coli 10 mg/kg and L-NIO 10 mg/kg. The control group was administered an IP and an SC injection of 0.9% NaCl. Each group received both injections at 24 and 16 hours before surgery. All rats underwent a 3-cm dorsal midline incision, which was subsequently closed. Five days after surgery, all rats were euthanized and skin from the healing wound was excised. Hydroxyproline levels and tensile strength were then measured.Results:
Forty-four male rats (mean age, 16 weeks; mean [SD] weight, 284 [16] g) were included in the study. Each of the groups receiving endotoxin (endotoxin, L-NAME, and L-NIO groups) had 12 rats; the control group consisted of 8 rats. All the groups that received endotoxin showed significant declines in hydroxyproline levels versus controls (P < 0.001, P = 0.001, and P = 0.002, respectively). Compared with the control group, the endotoxin-only group had a significant reduction in both mean (SD) hydroxyproline levels and mean (SD) wound tensile strength (298.27 [17.66] vs 175.82 [18.73] g/cm2 and 7.16 [0.51] vs 4.01 [0.29] μg/mg wet tissue; both, P < 0.001). Compared with the endotoxin- only group, rats that received L-NIO had significantly greater mean (SD) hydroxyproline levels and mean (SD) wound tensile strength (6.44 [0.34] vs 4.01 [0.29] μg/mg wet tissue and 280.12 [14.38] vs 175.82 [18.73] g/cm2; both, P < 0.001). Wound tensile strength in the L-NIO group was not significantly different from that in the control group. A significant difference was observed between the L-NIO and L-NAME groups in wound tensile strength (280.12 [14.38] vs 241.38 [20.69] g/cm2; P = 0.001), but not in tissue hydroxyproline levels.Conclusion:
Inhibition of NO synthesis might improve wound tensile strength, which suggests a possible role for NO inhibitors in improved wound healing in the presence of endotoxemia. 相似文献5.
Hayashi T Yano K Matsui-Hirai H Yokoo H Hattori Y Iguchi A 《Pharmacology & therapeutics》2008,120(3):333-339
Cellular senescence is characterized by permanent exit from the cell cycle and the appearance of distinct morphological and functional changes associated with an impairment of cellular homeostasis. Many studies support the occurrence of vascular endothelial cell senescence in vivo, and the senescent phenotype of endothelial cells can be transformed from anti-atherosclerotic to pro-atherosclerotic. Thus, endothelial cell senescence promotes endothelial dysfunction and may contribute to the pathogenesis of age-associated vascular disorders. Emerging evidence suggests that increasing nitric oxide (NO) bioavailability or endothelial NO synthase (eNOS) activity activates telomerase and delays endothelial cell senescence. In this review, we discuss the potential mechanisms underlying the ability of NO to prevent endothelial cell senescence and describe the possible changes in the NO-mediated anti-senescence effect under pathophysiological conditions, including oxidative stress and hyperglycemia. Further understanding of the mechanisms underlying the anti-senescence effect of NO in endothelial cells will provide insights into the potential of eNOS-based anti-senescence therapy for age-associated vascular disorders. 相似文献
6.
Nitric oxide: an ubiquitous messenger 总被引:10,自引:0,他引:10
A. Berdeaux 《Fundamental & clinical pharmacology》1993,7(8):401-411
Summary— During the last decade, a multitude of experimental arguments have led to the concept that EDRF is nitric oxide (NO), a messenger not only involved in the control of vasomotor tone but also in vascular homeostasis, neuronal and immunological functions. Regardless of its origin, endogenous NO is produced through the conversion of L-arginine to L-citrulline by NO-synthase (NOS) from which several isoforms have recently been isolated, purified and cloned. NOS-type I (isolated from brain) and type III (isolated from endothelial cells) are termed “constitutive-NOS” and produce picomolar levels of NO from which only a small fraction elicits physiological responses. These isoforms are regulated by Ca2+-calmodulin with NADPH, FAD/FMN and tetrahydrobiopterin as co-factors and reveal a high degree of homology with the amino-acid sequence of cytochrome P450 reductase within the C-terminal domain. Functionally, neuronal-NOS type I is important in neurotransmission (modulation of NMDA receptor), the central control of vascular homeostasis and possibly learning and memory. In the peripheral nervous system, NOS appears to be linked to nonadrenergic noncho-linergic (NANC) neuronal pathways. Endothelial-NOS type III is essential for the control of vascular tone in response to the release of endogenous mediators, although shear stress is the major trigger of endothelial-NOS activity under physiological conditions. NOS-type III also contributes to the prevention of abnormal platelet aggregation. NOS-types II and IV (isolated from macrophages) are Ca2+-calmodulin independent and are termed “inducible-NOS” since their activation is only promoted under pathophysiological situations where macrophages exert cytotoxic effects in response to cytokines. In contrast with NOS-types I and III, activation of NOS-type II in these cells induces the formation of nanomolar levels of NO which act as a defense mechanism of the immune system. Dysfunctions of the L-arginine-NO pathway have been characterized in multiple diseases (atherosclerosis, hypertension, diabete, sepsis, cerebral ischemia, etc) and the design of more selective activators/inhibitors of NOS isoforms is a new challenge for the understanding of their pathophysiology and treatment. 相似文献
7.
目的通过测定首发精神分裂症患者和正常人的血清一氧化氮合酶(NOS)活性,比较和分析他们之间的差异,探讨NOS活性以及一氧化氮(NO)能神经系统的功能变化与精神分裂症的关系。方法采用比色法分别测定首发未用抗精神病药的精神分裂症患者(研究组)、临床症状缓解的精神分裂症患者(缓解组)和正常对照者的血清NOS活性。结果研究组的血清NOS活性为6.3665±1.2260(n=39),明显高于症状缓解组(4.1204±0.9908,n=27,P<0.01)和正常对照组(3.2660±1.0320,n=27,P<0.01);症状缓解组的NOS活性也明显高于正常对照组(P<0.01)。结论精神分裂症患者血清NOS活性明显增高,L-精氨酸-NO神经通路功能的紊乱可能是精神分裂症的发病机制之一,也可能成为一个新的治疗靶系统。 相似文献
8.
Mervi R. H. Väisänen‐Tommiska 《Annals of medicine》2013,45(1):45-55
The human uterine cervix can produce nitric oxide (NO), a free radical with an ultra‐short half‐life. The release of NO changes during pregnancy and is increased in early nonviable pregnancies compared to normal uncomplicated pregnancies. This review concentrates on the role of NO release in cervical ripening in pregnant women. Also some suggestions on future aspects are discussed. 相似文献
9.
Aims and objectives. This paper, therefore, aimed to review published literature in this area of pharmacological exploitation, to look at the therapeutic applications and clinical relevance and, by so doing, provide an accessible source for nurses to gain insight into the role of nitric oxide in the clinical setting. Background. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function; a major endogenous regulator of vascular tone. The use of nitrates are well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide. Although widely addressed within the medical literature, there appears to be a paucity of nursing literature that explores either its physiological action, or its relevance to nursing practice. Conclusions. This literature review provides an overview of the use of nitric oxide and its implications for nursing practice and patient outcomes. Relevance to clinical practice. Knowledge of nitric oxide and its action is pertinent to nurses across diverse specialities. It helps in understanding the principles of many nitrogen‐derived medications which nurses administer to their patients on a daily basis. In terms of oral medication, this is demonstrated by greater insights into the action of nitrates, the appreciation of surprising developments in medications such as sildenafil and the development of new drug opportunities such as nitric oxide–non‐steroidal anti‐inflammatory drugs. Equally, the use of inhaled nitric oxide therapy in adult and neonatal critical care units appears to be an increasingly valuable source of treatment. A particular research challenge is found in the attempt at nitric oxide inhibition in the management of septic shock. The authors argue that understanding such esoteric areas of therapeutic developments is increasingly to be part of the repertoire of knowledge and skills for nurses in the 21st century. 相似文献
10.
Nitric oxide and the control of renin secretion 总被引:3,自引:0,他引:3
Summary— Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituitary and other endocrine glands, and evidence is accumulating that it contributes to the regulation of the secretion of renin by the kidneys. The enzyme nitric oxide synthetase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa , a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney and is responsive to changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro , suggesting a stimulatory role for the L-arginine-nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa and beta adrenoceptor mechanisms that regulate renin secretion. Future research should clarify the mechanisms by which nitric oxide regulates the secretion of renin and establish the physiological significance of this regulation. 相似文献
11.
脑梗死患者一氧化氮合酶基因多态性及其对一氧化氮的影响 总被引:1,自引:0,他引:1
目的观察脑梗死患者内皮型一氧化氮合酶(eNOS)基因多态性及一氧化氮(NO)变化情况。方法采用前瞻性病例对照研究,脑梗死组193例,均为发病2周内经头颅CT或MRI证实存在颈内动脉分布区梗死灶者,对照组103例为正常体检者。对两组eNOS基因4号内含子多态性进行测定,并采用Griess重氮化反应法和酶标法分别检测血清NO含量、NOS活性。结果脑梗死组eNOS基因4号内含子a等位基因(eNOS4a)携带者48例,对照组为12例,携带频率有显著性差异(χ2=8.86,P=0.003);经Logistic回归分析,eNOS4a携带是脑梗死的独立危险因素(P=0.032);脑梗死组NO产物浓度中位数为6.04(3.83~11.49)μmol/L,低于对照组6.89(4.64~12.43)μmol/L(P=0.022)。eNOS4a携带者NO产物浓度中位数为5.07(3.18~7.62)μmol/L,低于非携带者6.86(4.39~11.76)μmol/L(P=0.001)。脑梗死组NOS活性为(2.97±1.47)U/ml,对照组(3.16±1.46)U/ml,无显著性差异(P=0.517)。eNOS4a携带者NOS活性(2.77±1.13)U/ml,与非携带者(3.12±1.54)U/ml无显著性差异(P=0.100)。结论eNOS4a携带可能通过减少NO生成而在脑梗死发生过程中发挥作用。 相似文献
12.
大鼠创伤性脑水肿一氧化氮及其合成酶的变化 总被引:2,自引:0,他引:2
目的:探讨脑损伤后一氧化氮(NO)及一氧化氮合酶(NOS)与脑水肿的关系。方法:建立大鼠创伤性脑水肿模型,按不同时间点处死动物,测定其脑含水量及静脉血NO 和脑组织中NOS。结果:脑创伤后脑含水量随静脉血NO的增加而增加,组织NOS则随NO 的增加而下降。结论:创伤性脑水肿与血NO 有密切相关性,组织中NOS则是该过程的可能催化剂 相似文献
13.
Wallis JP 《Transfusion medicine (Oxford, England)》2005,15(1):1-11
Nitric oxide (NO) was identified as a physiological mediator of vascular tone in 1987. NO produced by endothelial cells causes vasodilatation and also inhibits platelet aggregation and leucocyte adhesion. Red cells metabolize NO to nitrate but may possibly carry and release, or even produce, NO in hypoxic conditions. NO physiology may have important implications for transfusion medicine, ranging from adverse effects of haemoglobin substitutes to preservation of stored platelets and to detrimental effects of stored red cells. 相似文献
14.
目的通过建立大鼠支气管哮喘模型,观察不同浓度氯胺酮对哮喘大鼠肺组织iNOS活性及NO含量的影响。方法SD大鼠随机分成对照组(N组)、哮喘模型组(A组)、不同浓度氯胺酮预处理组(分别为K1组、K2组)和地塞米松组(D组),每组8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发哮喘;氯胺酮处理组大鼠用同样方法致敏,但在激发前分别给予雾化吸入氯胺酮25 g/L(K1组)和50 g/L(K2组);D组在激发前给予雾化吸入0.01%地塞米松;N组用生理盐水替代卵蛋白进行注射和吸入。每组分别测定其肺组织NO2-/NO3-水平、肺组织诱导型NOS(iNOS)和原生型NOS(cNOS)活性水平,并用免疫组织化学法观察iNOS在大鼠哮喘模型肺组织中的分布。结果A组肺组织中NO2-/NO3-和iNOS水平升高,iNOS和肺组织NO2-/NO3-水平呈高度正相关;K1、K2组肺组织中NO2-/NO3-和iNOS水平低于A组(P<0.05);D组肺组织中NO2-/NO3-和iNOS水平亦低于A组(P<0.05)。结论25 g/L或50 g/L的氯胺酮雾化吸入可抑制哮喘大鼠肺组织iNOS活性,降低NO含量,减轻大鼠肺部炎症。 相似文献
15.
O. D. Altland D. Dalecki V. N. Suchkova C. W. Francis 《Journal of thrombosis and haemostasis》2004,2(4):637-643
Summary. Low‐intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)‐dependent mechanism. We have developed a model to expose endothelial cells to well‐characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature‐controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm?2 for 10 min increased HUVEC media NO by 102 ± 19% (P < 0.05) and BAEC by 117 ± 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 ± 24% in HUVEC and by 32 ± 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post‐exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 ± 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm?2 (P < 0.01) and a maximum response at 0.125 W cm?2. US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low‐intensity, low‐frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically. 相似文献
16.
目的:探讨外源性L-精氨酸(L-Arg)对移植血管诱导型一氧化氮合酶活性影响,方法:新西兰大白兔15只随机分成3组,建立双侧颈动脉间置颈外静脉移植动物模型,高剂量组每日喂食L-Arg 250mg/kg,低剂量组每日喂食L-Arg 125mg/kg,对照组不喂食L-Arg,持续2周,观察移植血管术前,术后3周和术后6周血浆一氧化氮(NO)水平,组织匀浆一氧化氮合酶(NOS)活性和诱导型NOS的mRNA表达。结果:(1)血浆NO水平:实验组血浆NO水平显著高于对照组,高剂量组血浆NO水平高于低剂量组。(2)组织匀浆NOS活性:实验组组织匀浆NOS活性显著高于对照组,3组术后6周NOS活性高于术后3周。(3)组织匀浆iNOS mRNA表达:术后3周实验组iNOS mRNA表达,对照组无表达;术后6周3组iNOS mRNA均有表达,实验组iNOS mRNA表达高于对照组,高剂量组高于低剂量组,结论:外源性L-Arg促进移植血管NOS表达,增进NOS活性,提高体内NO浓度。 相似文献
17.
目的:探讨精氨酸酶2(arginase-2,Arg-2)和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在肝细胞肝癌(hepatocellular carcinoma,HCC)中的表达及其与肿瘤血管形成的相关性。方法:采用免疫组化方法检测158例HCC患者手术切除标本中Arg-2、iNOS的表达,抗CD34单克隆抗体显示血管内皮细胞。采用Image-Pro plus 6.2.1图像分析软件测定肿瘤微血管密度(microvessel density,MVD)。结果:158例HCC中,Arg-2、iNOS的阳性表达率分别为73.4%(116/158)、83.5%(132/158)。Arg-2和iNOS在HCC组织中的表达正相关(r=0.474,P=0.000)。116例Arg-2阳性HCC组织的MVD为(283.92±130.69)/0.702mm~2,42例Arg-2阴性HCC组织的MVD为(129.25±51.00)/0.702mm~2,差异有统计学意义(P=0.000);132例iNOS阳性组织的MVD为(267±131.49)/0.702mm~2,26例iNOS阴性HCC组织的MVD为(116±41.85)/0.702mm~2,差异有统计学意义(P=0.000)。结论:Arg-2与iNOS在HCC组织中的表达正相关,且与MVD相关,提示Arg-2与iNOS可能参与调节HCC中微血管的形成。 相似文献
18.
《Annals of medicine》2013,45(7):694-716
AbstractThe present review first summarizes the complex chain of events, in endothelial and vascular smooth muscle cells, that leads to endothelium-dependent relaxations (vasodilatations) due to the generation of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) and how therapeutic interventions may improve the bioavailability of NO and thus prevent/cure endothelial dysfunction. Then, the role of other endothelium-derived mediators (endothelium-derived hyperpolarizing (EDHF) and contracting (EDCF) factors, endothelin-1) and signals (myoendothelial coupling) is summarized also, with special emphasis on their interaction(s) with the NO pathway, which make the latter not only a major mediator but also a key regulator of endothelium-dependent responses. 相似文献
19.
目的探讨辛伐他汀纳米粒对脓毒症相关急性肺损伤小鼠肺组织中诱导型一氧化氮合酶(iNOS)/内皮型一氧化氮合酶(eNOS)平衡的调节以及对脓毒症小鼠预后的影响。
方法将90只C57 / BL6小鼠分为假手术组、脓毒症组、灌胃组、静脉制剂组及纳米粒组,每组各18只。采用盲肠结扎穿孔术(CLP)建立脓毒症小鼠模型;灌胃组小鼠通过灌胃针,给予辛伐他汀口服制剂灌胃治疗后进行CLP术;静脉制剂组及纳米粒制剂组小鼠CLP术后,立即分别通过尾静脉注射预配置好的辛伐他汀静脉制剂和辛伐他汀纳米粒制剂。其中每组12只小鼠用于7 d生存评估,另外6只用于24 h时间点标本采集。每24小时观察小鼠的生存情况,然后记算各组小鼠每日生存情况。采用苏木素-伊红(HE)染色观察5组小鼠病理变化并计算肺损伤病理评分,免疫组织化学法检测5组小鼠肺组织iNOS、eNOS表达水平。
结果Kaplan-Meier生存曲线结果显示,5组小鼠7 d生存情况比较,差异有统计学意义(χ2 = 3.780,P < 0.001)。进一步两两比较发现,脓毒症组及灌胃组小鼠的7 d生存情况均较假手术组明显下降(P均< 0.001),而纳米粒组小鼠的7 d生存情况显著优于脓毒症组(P = 0.001)。HE染色结果显示,假手术组小鼠肺组织未见明显病理征象;脓毒症组小鼠肺组织弥漫性中性粒细胞浸润、肺泡腔变小、肺泡间中隔增厚、肺间质弥漫性水肿、细胞排列紊乱、部分肺组织完整性遭破坏;灌胃组小鼠病理所示与脓毒症组相似;静脉制剂组及纳米粒组小鼠中性粒细胞渗出均较脓毒症组损伤减少、肺泡完整性较好、损伤程度较轻。5组小鼠肺损伤病理评分、iNOS及eNOS表达水平比较,差异均有统计学意义(F = 889.200、9.633、6.918,P均< 0.05)。进一步两两比较发现,脓毒症组小鼠的肺损伤病理评分、iNOS及eNOS表达水平与假手术组比较,差异均有统计学意义(P均< 0.05);静脉制剂组及纳米粒组小鼠病理评分、iNOS及eNOS表达水平与脓毒症组比较,差异均有统计学意义(P均< 0.05),且纳米粒组小鼠的肺损伤病理评分较静脉制剂组显著降低(P < 0.05)。
结论不同的辛伐他汀制剂具有不同的效应,其中纳米粒制剂对于脓毒症相关的肺损伤最具保护价值,建立eNOS与iNOS之间的平衡,可以成为具有保护效应的重要处理位点。 相似文献
20.
NOS及NO在介导Aβ神经毒性和阿尔茨海默病发病机制中的作用 总被引:5,自引:5,他引:5
目的观察诱导型一氧化氮合酶(iNOS)抑制剂胍氨酸(AG)及神经元型一氧化氮合酶(nNOS)抑制剂7-硝基吲哚(7-NI)对β淀粉样蛋白1-40(Aβ1-40)在体神经毒性的干预,进一步探讨一氧化氮合酶(NOS)及一氧化氮(NO)在Aβ神经毒性和Alzheimer病(AD)发病机制中的介导作用。方法雄性SD大鼠35只,随机分为正常对照,生理盐水注射,Aβ1-40注射,AG+Aβ1-40,7-NI+Aβ1-40,花生油(Peanutoil,PO)+Aβ1-40、生理盐水+Aβ1-40共7组,每组5只。观察各组大鼠的Y迷宫学习记忆作业及局部神经元损伤情况。结果Aβ1-40海马组大鼠Y迷宫作业的获得和再现尝试次数均显著增加,分别是(27.8±2.3)和(19.7±4.7)次,与前两组比较有显著性意义(F获得=146.438,P获得=0.000;F再现=113.654,P再现=0.000)。海马齿状回颗粒细胞背侧带受损长度为(1.93±0.26)mm,局部胶质细胞反应明显。AG可逆转Aβ1-40导致的学习记忆和神经元损伤,其获得和再现尝试次数分别为(14.6±4.9)次和(8.5±2.1)次,与Aβ1-40注射组比较明显减少(F获得=146.438,P获得=0.000;F再现=113.654,P再现=0.000)。细胞带受损长度为(0.41±0.21)mm,胶质细胞反应减轻。7-NI则无干预作用。结论iNOS/NO参与了在体条件下对Aβ神经毒性的介导,在AD发病机制中具有重要作用。 相似文献