Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.

Role of nitric oxide in hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.

Effect of a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on invasion of human colorectal cancer cell line SL-174T

AIML To investigate the effect and mechanism of action of the nitric oxide synthase （NOS） inhibitor NG-nitro-L-arginine methyl ester （L-NAME） on invasion and metastasis of human colorectal cancer cell line SL-174T. METHODS： Human colorectal cancer cel4 line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h, Nitric oxide （NO） production was measured with Griess reagent, The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane （Matrigel）, RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor metalloproteinase-2 （TIMP-2）,RESULTS： L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L- NAME, respectively, the ability of the L-NAME treated SL- 174T cells to invade the reconstituted basement membrane decreased significantly （t = 8.056, P〈0.05; t= 14.467, P〈0.01; t= 27.785, P〈0.01; and t= 29.405, P〈0.01, respectively） and the inhibition rates were 10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46. 85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively （t = 15.116, P〈0.01）. In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased （t = 71.238, P〈0.01） and that of TIMP-2 mRNA was markedly increased （t = -13.020, P〈0.01）. CONCLUSION： L-NAME exerts anti-invasive and anti- metastatic effects on SL-174T cell line via downregulating MNP-2 mRNA expression and upregulating TIMP-2 mRNA expression.

Bioinformatics analysis and prediction for structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei

ObjectiveTo search and analyze nitric oxide synthase (NOS) and similar proteins from Plasmodium berghei(Pb).MethodsThe structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics.ResultsPbNOS were not available, but nicotinamide adenine dinucleotide 2′–phosphate reduced tetrasodium (NADPH)–cytochrome p450 reductase(CPR) were gained. PbCPR was in the nucleus of Plasmodium berghei, while 134aa–229aa domain was localize in nucleolar organizer. The amino acids sequence of PbCPR had the closest genetic relationship with Plasmodium vivax showing a 73% homology. The tertiary structure of PbCPR displayed the forcep–shape with wings, but no wings existed in the tertiary structure of its' host, Mus musculus(Mm). 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR showed no homology with MmCPRs', and all domains were exposed on the surface of the protein.ConclusionsNOS can't be found in Plasmodium berghei and other Plasmodium species. PbCPR may be a possible resistance site of antimalarial drug, and the targets of antimalarial drug and vaccine. It may be also one of the mechanisms of immune evasion. This study on Plasmodium berghei may be more suitable to Plasmodium vivax. And 137aa–200aa, 201aa–218aa, 220aa–230aa, 232aa–248, 269aa–323aa, 478aa–501aa and 592aa–606aa domains of PbCPR are more ideal targets of antimalarial drug and vaccine.

Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.

Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.

Doxorubicin hydrochloride and L-arginine co-loaded nanovesicle for drug resistance reversal stimulated by near-infrared light

Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.

The immune function injury and its mechanism in drug abuser

Objective To explore the immune function injur y and its mechanism in drug abuser.Methods The immune function changes in50drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells,transformation rate of lymphocytes,IgA,IgM,IgG,IgE,com pliment C 3 ,C 4 ,IL-1,IL-2,IL-6TNF and NO.Result In peripheral blood the percentage o f Th 1 cell,transformation rate of lymphocyte,IgA,IgM,IgG,IgE content,complime nt C4,C4,IL-1,IL-2,IL-6,and TNF le vels were significantly lower than normal (P <0.01).The value of Th 1 /Th 2 was lower than normal as well(P <0.05).NO content was significantly higher than normal (P <0.001).Conclusion The mechanism of immune function inj ury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymu s-hypothalamus-hypophysis-adren al axis.

Novel Solid State Nitric Oxide Sensor Using Siloxane-Poly(Oxypropylene)(PPO)

In this paper, a novel solid state Nitric Oxide (NO) sensor made of a spin trap (iron(II)-diethyldithiocarbamate complex, FeDETC) encapsulated in a siloxane-poly(oxypropylene) (PPO) matrix was developed. Nitric oxide (NO), a free radical molecule, has numerous roles in various physiological functions, such as the regulation of blood pressure, immune response to bacterial infection, and nervous systems. Siloxane-polyether hybrid materials, for example siloxane-poly(oxypropylene) (PPO), are easy to prepare, transparent and flexible. The combination of all these characteristics in a unique material allows it to be used in several scientific and technological areas, including human health. NO radical is trapped in FeDETC, which allows its detection by electron paramagnetic resonance (EPR). FeDETC was added while PPO was a sol, which was then left in air for gelation. The novel sensor was dived directly into a solution of NO, when the NO-FeDETC complex was formed. Our results show that the novel sensor responds to NO, with similar sensitivity as previously published sensors. PPO sensors present a strong EPR signal and a high stability, keeping its signal for 45 days. We have studied ways to accelerate the NO release from the sensor, in order to study its potential as a drug delivery system. We observed an acceleration in NO release by using a modulated magnetic field of 40 G at 100 kHz;as well as by UV irradiation. Thermal induced NO release was also tested by heating NO-FeDETC PPO up to 50°C, with good results.

EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE GENE EXPRESSION OF NITRIC OXIDE SYNTHASE IN ISCHEMIC RAT BRAINS

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains during ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P

黄酮类NO供体纳米颗粒通过调控巨噬细胞极化促进PDLSCs成骨分化的体外研究

目的一氧化氮(nitric oxide,NO)作为一种信号分子,调节关键生理过程,与牙周炎关系密切。本研究拟探讨负载黄酮类NO供体药物的复合纳米颗粒(G10@HAP/MSN@ZnO@COS)通过调控巨噬细胞极化对牙周膜干细胞(periodontal liga⁃ment stem cells,PDLSCs)成骨分化的影响。方法将新型NO供体药物G10负载于羟基磷灰石掺杂的介孔二氧化硅颗粒(hydroxyapatite/mesoporous silica nanoparticles,HAP/MSN)上,并用氧化锌(zinc oxide,ZnO)填充,再通过壳聚糖(chitosan,COS)包裹,制备复合纳米颗粒(G10@HAP/MSN@ZnO@COS)。CCK⁃8细胞实验筛选G10@HAP/MSN@ZnO@COS促进细胞增殖的最佳浓度。通过脂多糖刺激小鼠单核巨噬细胞建立细胞炎症模型后,将其分为Control组、G10组、HAP/MSN@ZnO@COS组和G10@HAP/MSN@ZnO@COS组,各组分别加入新鲜培养基、5μg/mL G10、5μg/mL HAP/MSN@ZnO@COS和5μg/mL G10@HAP/MSN@ZnO@COS,培养72 h,采用ELISA和RT⁃qPCR检测各组细胞因子(TNF⁃α、IL⁃6、IL⁃1β、iNOS、IL⁃10)的表达水平,评估其M1/M2表型变化。用各组培养基上清液作为条件培养基培养PDLSCs,并通过碱性磷酸酶活性检测和茜素红染色评估其成骨矿化能力。结果CCK⁃8实验显示,5μg/mL G10@HAP/MSN@ZnO@COS能显著促进PDLSCs的增殖。ELISA结果表明,与Control组相比,G10@HAP/MSN@ZnO@COS组中M1型标志物IL⁃1β、IL⁃6、TNF⁃α和iNOS的表达显著降低(P<0.0001),而M2型标志物IL⁃10表达显著升高(P<0.0001)。RT⁃qPCR结果与ELISA结果一致,显示G10@HAP/MSN@ZnO@COS组中M1相关基因的表达显著下降(P<0.01)。在G10@HAP/MSN@ZnO@COS调控巨噬细胞的环境下,茜素红染色和碱性磷酸酶活性检测结果表明,G10@HAP/MSN@ZnO@COS⁃CM作为条件培养基,PDLSCs的矿化结节数量和碱性磷酸酶活性均显著高于其他组(P<0.0001)。结论复合纳米颗粒(G10@HAP/MSN@ZnO@COS)能有效抑制巨噬细胞向M1表型极化,并促进其向M2表型极化,G10@HAP/MSN@ZnO@COS调控的抗炎微环境能增强PDLSCs的成骨分化能力。

一氧化氮供体型药物对牙龈卟啉单胞菌体外抗菌活性的影响

目的研究一氧化氮(nitric oxide,NO)供体型药物对牙龈卟啉单胞菌(Porphyromonas gingivalis,P.g)体外抗菌活性的影响。方法采用菌落计数法、总NO检测试剂盒、活性氧检测试剂盒、钙离子(Ca^(2+))荧光探针Fluo-4 AM检测不同浓度的NO(10、30、50 mmol/L)对P.g的体外抗菌性能,以及对P.g胞内活性氧(reactive oxygen species,ROS)水平和Ca^(2+)浓度的影响。结果NO对P.g有显著的体外抗菌活性,并且其抗菌活性与NO药物浓度和作用时间具有明显的正相关性(P<0.05)。NO处理后显著提高了P.g胞内ROS水平和Ca^(2+)浓度(P<0.05)。结论NO能够有效抑制P.g的活性和生长能力,并引起P.g胞内ROS和Ca^(2+)代谢紊乱。NO供体型药物对种植体周围炎具有潜在的治疗作用和临床应用价值。

胆汁酸为载体的肝靶向一氧化氮释放药物的设计与合成

新型肝靶向一氧化氮释放药物对许多肝脏疾病具有较好的治疗作用.以胆酸和熊去氧胆酸作为药物的载体,以氨基酸作为联接子,以氨基酸的α羧基模拟胆酸或熊去氧胆酸分子24位羧基的负电性,最大限度地保持胆酸或熊去氧胆酸的结构特征,通过酰胺键将载体与一氧化氮供体硝酸酯偶联,设计并合成了一系列新型肝靶向一氧化氮释放偶合物,其结构经元素分析,IR,1H NMR和MS光谱分析确证.利用四氯化碳及对乙酰氨基酚所致小鼠急性肝损伤模型研究化合物对小鼠急性肝损伤的修复作用.

活血化瘀汤影响骨折愈合早期一氧化氮合酶活性的作用机制探讨

目的 :检测骨折愈合早期大鼠血清一氧化氮合酶 (NOS)及其异构体的酶活性及活血化瘀汤对其的影响。方法 :选用雄性SD大鼠 2 0只 ,建立胫骨中段标准骨折模型 ,随机分为两组 ,每组 10只 ,分别以活血化瘀汤灌胃 (中药组 )或生理盐水灌胃 (对照组 ) ;采用化学比色法测定骨折后 1、4、7、14、2 1dNOS总量、诱导型一氧化氮合酶 (iNOS)及原生型一氧化氮合酶 (cNOS)的活性。结果 :骨折愈合早期血清cNOS酶活性增强 ,骨折后 4d达峰值。血清iNOS酶活性于骨折后 14d达峰值 ;中药组NOS酶总量维持在较高水平 ,cNOS酶活性于骨折后 14d达到峰值。两组比较 ,骨折后 7、14、2 1d血清NOS总量及骨折后 14dcNOS酶活性提高非常显著 (P <0 0 1) ,4dNOS总量、7dcNOS酶活性显著提高 (P <0 0 5 )。血清iNOS酶活性在骨折后 4、7、2 1d中药组高于对照组 ,1、14d低于对照组 ,但无统计学意义。结论 :骨折愈合早期血清NOS酶活性随时间变化 ,不同的异构体变化不同 ;活血化瘀汤能激活大鼠骨折后血清NOS酶活性的作用 ,对不同的NOS同工酶在不同的时间产生的作用不同。提示活血化瘀汤可通过不同方式激活NOS酶活性促进骨折愈合。

养心康对心功能不全动物模型的血流动力学研究

目的 :建立心功能不全的动物模型 ,探讨养心康在血流动力学方面的作用及其作用机理。方法 :通过增加腹主动脉压力负荷而建立心功能不全的兔模型 ,以高、低两种不同剂量的养心康治疗 2 0d ,以心宝作为药物对照 ,并设立模型对照和空白对照 ,观察各组模型血流动力学指标及血液中一氧化氮水平在治疗前后的变化。结果 :大剂量养心康能明显降低心衰模型的心率、收缩压、左室舒张末压 (LVEDP) ,心室等容收缩期中室内压上升的最大速率 ( +dp/dtmax)及心室等容舒张期中室内压下降的最大速率 ( -dp/dtmax) ,且呈剂量依赖性 ,与心宝对照组相比具有显著性差异。结论 :养心康能剂量依赖性地改善心衰模型的血流动力学指标 ,延缓心衰的进程 。

黄芩含药血清对3种巨噬细胞的抗炎免疫活性

目的考察黄芩提取物（SBE）含药血清对正常的及细菌脂多糖（LPS）激活的3种单核巨噬细胞一氧化氮（NO）释放的影响。方法将SBE灌胃大鼠后,在0.5~6 h内,眼眶取血,分离血清,将血清加入正常的及LPS活化的3种巨噬细胞培养液内,培养24 h后,检测培养液内NO含量。结果 SEB不同给药时间的含药血清,在不影响细胞存活率的情况下,可以不同程度的降低正常的及LPS激活的3种巨噬细胞NO的释放量。结论 SBE含药血清具有一定的免疫抑制及抗炎活性。

巴戟素补肾健脑作用的神经活动基础

巴戟素是广州中医药大学新近从补肾中药巴戟天中提取的一种糖类单体物。为探讨巴戟素的补肾健脑的神经作用机制， 本实验以大鼠离体海马脑片为标本， 从细胞分子水平上观察巴戟素对大鼠海马脑片缺氧状态下的诱发群锋电位（ｐｏｐｕｌａｔｉｏｎ ｓｐｉｋｅ， ＰＳ） 和突触传递长时程增强（ｌｏｎｇ ｔｅｒｍ ｐｏｔｅｎｔｉａｔｉｏｎ ， ＬＴＰ） 的影响。结果观察到巴戟素对脑缺氧损伤具有保护作用， 并能增强脑的记忆功能； 并观察到其作用机制与一氧化氮（ＮＯ） 有一定关系。实验结果从神经活动角度为中医补肾健脑理论增补了现代科学内容，

雷公藤内酯醇抑制滑膜成纤维细胞COX-2和iNOS表达

目的 :研究雷公藤内酯醇对类风湿关节炎滑膜成纤维细胞 (RASF)增殖和表达环氧化酶 - 2 (COX- 2 )、诱导型一氧化氮合酶 (i NOS)及合成前列腺素 E2 (PGE2 )、一氧化氮 (NO)的影响 ,并探讨其机制。方法 :分离培养人类风湿关节炎滑膜成纤维细胞 ,用 TNFα(2 0μg/ L)刺激 ,同时加或不加雷公藤内酯醇 (TP,0～ 10 0μg/ L )。分别用 3 H-Td R法、竞争酶联免疫吸附试验 (ELISA)和硝酸酶还原法、半定量逆转录 -聚合酶联反应 (RT- PCR)法、细胞酶免疫法及蛋白免疫印迹 (Western- blot)法 ,检测滑膜细胞的增殖活性、细胞培养上清液中 PGE2和 NO的水平 ,滑膜细胞 COX- 2和 i NOSm RNA表达水平及蛋白表达水平。同时提取各组细胞蛋白 ,测定其核转录因子 NF-κB活性。结果 :TP(>2 0μg/ L)能显著抑制 TNFα诱导的 RASF COX- 2和 i NOS表达 ,并明显减少 PGE2和 NO的生成 ,抑制作用与 TP浓度呈明显相关性。同时观察到 ,TP对 TNFα激活的 RASF核转录因子 NF- κB活性有明显的抑制作用(IC50 ≈ 35 μg/ L) ,TP对 RASF NF- κB活性的抑制程度与其抑制 RASF COX- 2和 i NOS表达的效应相一致。实验未观察到 TP对 RASF增殖的影响。结论 :TP可显著抑制 TNFα刺激的 RASF COX- 2和 i NOS的表达及其诱导产物PGE2和 NO的生成 ,这?

螺旋藻改善铝中毒小鼠学习记忆障碍机制探讨

目的:探讨螺旋藻改善铝中毒小鼠学习记忆障碍的作用机制。方法:用口服氯化铝方法建立小鼠铝中毒学习记忆障碍模型,并用螺旋藻多糖灌胃进行实验性治疗。用跳台试验和避暗试验检测各组小鼠的学习记忆行为,并用免疫组化ABC法检测各组小鼠海马神经元型一氧化氮合酶(nNOS)的表达。结果:与对照组比较,模型组小鼠表现出明显的学习记忆障碍,海马nNOS表达下降。实验组的学习记忆能力较模型组有明显改善,海马nNOS表达增加。结论:螺旋藻对铝中毒小鼠的学习记忆障碍有明显的改善作用,其作用机制可能与增加nNOS的表达有关。