热休克反应对高温诱导的低血压的保护作用及其机制

目的:探讨热休克反应对高温诱导的低血压的保护作用及机制.方法:给予热休克预处理,观察热休克大鼠致死热暴露后生存时间、血压动态变化及热暴露73 min时心肌一氧化氮含量.结果:热暴露后,热休克组血压显著高于对照组,而心肌一氧化氮含量却低于对照组.结论:HSR通过抑制热暴露大鼠心肌NO的过量生成,对高温诱导的低血压起到了明显的保护作用.     

外源性硫化氢对创伤失血性休克大鼠血浆炎症因子的影响

目的：研究外源性硫化氢（H2S）对创伤失血性休克大鼠炎症反应的影响。方法：选择健康成年雄性SD大鼠随机分为四组：假手术组（Sham）,模型组（HTS）,生理盐水组（NS）,NaHS处理组（NaHS）,采用创伤失血性休克模型,Sham组完成所有手术操作,但不放血和复苏,HTS组完成所有手术操作放血后给予Ringer＇s液复苏,NS组放血后在Ringer＇s液复苏前腹腔注射与NaHS组等容量的生理盐水,NaHS组在复苏前给与NaHS28μmol/kg（生理盐水稀释至0.5ml）腹腔注射。持续监测各组平均动脉压（MAP）及心律（HR）,并通过测定血浆中TNF-α、IL-1β、IL-6和IL-10浓度的变化,观察外源性硫化氢对创伤失血性休克大鼠血浆炎症因子的影响。结果：①与HTS组及NS组比较,NaHS组复苏后MAP明显改善（P〈0.05）。②与HTS组及NS组比较,复苏后1小时NaHS组血浆TNFα、IL-1β、IL-6浓度明显降低（P〈0.05）;而IL-10浓度四组间差异不明显（P〉0.05）。结论：外源性硫化氢可改善创伤失血性休克大鼠复苏后平均动脉压及抑制复苏后早期炎症反应。     

阿司匹林通过调节Hippo途径抑制大鼠颅内动脉瘤的形成和机制

摘要 目的：探讨阿司匹林通过调节Hippo途径抑制大鼠颅内动脉瘤形成的机制。方法：选择40只健康SD大鼠分为对照组（不做任何处理）、假手术组（暴露双侧肾动脉后支和左颈总动脉,但不结扎）、动脉瘤组（结扎双侧肾动脉后支和左颈总动脉后生理盐水灌胃）和阿司匹林组（动脉结扎后阿司匹林灌胃）,各10只。灌胃12周后检测血清炎性因子[肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）、IL-10]、血管内皮损伤标志物[一氧化氮（NO）、内皮素-1（ET-1）、血管内皮生长因子（VEGF）]。处死大鼠后,检测动脉瘤大小、壁厚比、内腔面积和中膜变薄长度,检测动脉瘤血管组织中Yes相关蛋白（YAP）表达情况。结果：（1）动脉瘤组和阿司匹林组大鼠Willis环上有明显凸起,且阿司匹林组大鼠凸起明显小于动脉瘤组。阿司匹林组大鼠动脉瘤大小、内腔面积和中膜变薄长度均显著小于动脉瘤组,壁厚比显著大于动脉瘤组（P＜0.05）。（2）动脉瘤组和阿司匹林组大鼠血清TNF-α、MCP-1、IL-6水平显著高于对照组和假手术组,IL-10水平显著低于对照组和假手术组（P<0.05）;阿司匹林组大鼠血清TNF-α、MCP-1、IL-6水平显著低于动脉瘤组,IL-10水平显著高于动脉瘤组（P<0.05）。（3）动脉瘤组和阿司匹林组大鼠血清NO水平显著低于对照组和假手术组,ET-1和VEGF水平显著高于对照组和假手术组（P<0.05）;阿司匹林组大鼠血清NO水平显著高于动脉瘤组,ET-1和VEGF水平显著低于动脉瘤组（P<0.05）。（4）动脉瘤组和阿司匹林组大鼠YAP蛋白表达相对吸光值显著高于对照组和假手术组（P<0.05）;阿司匹林组大鼠YAP蛋白表达相对吸光值显著低于动脉瘤组（P<0.05）。结论：阿司匹林能够显著减轻颅内动脉瘤大鼠炎性反应,改善血管内皮功能,抑制颅内动脉瘤形成,这可能与阿司匹林调控Hippo信号通路有关。     

诱导型一氧化氮合酶介导β淀粉样蛋白在体神经毒性

目的：探讨一氧化氮合酶（NOS）及一氧化氮（NO）在β淀粉样蛋白（Aβ）神经毒性和Alzheimer病（AD）发病机制中的介导作用。方法：应用行为学及病理学方法,观察海马注射Aβ1－40对大鼠Y迷宫学习记忆的影响及对局部神经元的损伤作用;观察特异性诱导型一氧化氮合酶（iNOS)抑制剂胍氢酶（AG）及特异性神经元型一氧化氮合酶(nNOS)抑制剂7－硝基吲哚（7－NI）腹腔注射对海马内注射Aβ1－40神经毒性的干预,结果：海马注射Aβ1－40后,大鼠Y迷宫学习记忆能力及海马局部神经元明显受损,特异性iNOS抑制剂AG能够阻止Aβ1－40海马注射对大鼠学习记忆和局部神经元的损伤作用,而特异性nNOS抑制剂7－NI无此干预效应。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。     

限制性液体复苏对失血性休克复苏患者血浆TNF-alpha、IL-6 水平的影响

目的：探究限制性液体复苏对失血性休克复苏患者血浆肿瘤坏死因子（TNF-alpha）、白细胞介素-6（IL-6）水平的影响,为临床治 疗失血性休克选择液体复苏方式提供依据。方法：选择2010 年1 月~2015 年6 月期间,我院收治出血性休克患者63例为研究对 象;采用随机数字法将其分为观察组（32 例）和对照组（31 例）,观察组患者给予限制性液体复苏,对照组患者给予传统充分复苏; 观察并比较两组患者治疗前后血浆TNF-alpha、IL-6 水平的变化。结果：观察组患者给予复苏液体的输入量为（1.95± 0.35）L,对照组 患者给予输液量为（3.61± 0.56）L,观察组患者给予的复苏液输入量显著低于对照组,差异具有统计学意义（P<0.05）;治疗前两组 患者血浆TNF-alpha及IL-6 水平不存在显著差异（P>0.05）;治疗后两组患者血浆TNF-alpha及IL-6 水平均显著上升,且观察组患者血浆 TNF-alpha及IL-6水平均显著低于对照组,差异具有统计学意义（P<0.05）。结论：限制性液体复苏能够明显降低失血性休克患者的出 血量,稳定机体血流动力学,保证机体重要脏器的血流灌注,有利于改善患者血浆TNF-琢和IL-6 水平,提高治疗效果,改善预后。     

纳洛酮对发热大鼠下丘脑中cAMP和腹中膈区AVP含量的影响

目的：研究纳洛酮对白细胞介素-1β（IL-1β）致热大鼠发热反应的影响及机制。方法：经大鼠侧脑室微量注射IL-1β建立发热模型,观察纳洛酮对发热大鼠体温的影响,并测定下丘脑中环磷酸腺苷（cAMP）和腹中膈区精氨酸加压素（AVP）含量。结果：纳洛酮减弱了IL-1β致热效应,同时下丘脑中cAMP和腹中膈区AVP含量也相应减少（P〈0．01）。结论：纳洛酮能够抑制大鼠IL-1β性发热,其机制可能是抑制下丘脑中cAMP的合成,并且促进腹中膈区AVP的释放。     

IL-1β对精氨酸升压素诱导的大鼠心肌成纤维细胞INOS-NO系统活性的影响

目的：探讨白细胞介素-1β（IL-1β）对精氨酸升压素（AVP）诱导下大鼠心肌成纤维细胞（CFs）诱导型一氧化氮合酶（iNOS）-一氧化氮（NO）系统活性的影响。方法：胰酶消化法分离培养SD仔鼠CFs,硝酸还原酶法、分光光度法和逆转录-聚合酶链式反应（RT—PCR）分别测定不同浓度IL-1β与AVP协同作用下CFs的NO含量、NOS活性和iNOSmRNA表达。结果：AVP诱导下CFs iNOSmRNA表达、NOS活性和NO合成均显著增加（P〈0.05）。一定浓度范围内IL-1β与AVP协同作用,剂量依赖性地增加AVP对CFs iNOS-NO系统活性的提高作用,其中AVP＋3ng／ml和AVP＋5ng／ml IL-1β组的iNOS mRNA表达、NOS活性和NO合成均显著高于AVP组（P〈0。05）,但IL-1β浓度增加至5ng／ml时,CFs的iNOSmRNA表达、NOS活性和NO合成不再继续升高,反而有所下降。结论：在一定浓度范围内IL-1β可与AVP协同提高CFs iNOS-NO系统活性。     

运动干预对胰岛素抵抗大鼠骨骼肌IL-1β表达的影响

目的观察运动干预对高脂饲料诱导胰岛素抵抗（IR）大鼠白细胞介素1β（IL-1β）表达的影响,探讨运动减轻IR的可能机制。方法健康Wistar雄性大鼠分为基础饲料喂养组（normal chow group,NC）,高脂膳食喂养组（high-fat diet group,HF）。高脂膳食喂养Wistar雄性大鼠10周,构建IR动物模型。10周后,HF组再随机分为高脂喂养运动组和非运动组,游泳运动干预4周。游泳运动干预前后以正常血糖-高血浆胰岛素钳夹实验技术[hyperinsulinemic-euglycemic clamp（HEC）technique]评估IR大鼠胰岛素敏感性,ELISA法测定大鼠血清IL-1β水平,RT-PCR法测定大鼠骨骼肌IL-1βmRNA表达。结果HF组大鼠葡萄糖输注率（glucose infusion rate,GIR）显著低于NC组（P〈0.05）,HF组血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显高于NC组（P〈0.05,P〈0.01）;运动组大鼠血清IL-1β水平及骨骼肌组织IL-1βmRNA表达明显低于非运动组（P〈0.05）,与NC组差异无显著性（P〉0.05）。结论运动改善IR大鼠胰岛素敏感性,可能与降低IR大鼠IL-1β的表达有关。     

白细胞介素-1β对实验性急性缺氧诱导的大鼠窦神经放电的影响

最近的研究显示,颈动脉体（carotid body,CB）除具有缺氧等化学感受功能外,还对白细胞介素-1B（IL-1β）的刺激起反应。但是,IL-1β刺激对颈动脉体的缺氧感受功能有何影响还不清楚。本研究运用在体（in vivo）细胞外神经干电位记录的方法,利用麻醉大鼠,观察了CB局部给予IL-1β对实验性急性缺氧（experimental acute hypoxia,EAH）诱导的CB传入神经窦神经（carotid sinus nerve,CSN）放电频率的影响。结果发现,EAH可以诱导麻醉状态下大鼠的CSN放电频率增高;颈动脉体局部给予ATP（0、1mmol／L）和ACh（0,5mmol／L）在一定程度上可模拟缺氧诱导的CSN放电;局部给予ILlp（40μg／L）可诱导窦神经放电频率增加。但同时给予IL-1B和EAH,所引起的放电频率增高效应与单独给予EAH或IL-1β所诱导的放电频率的增高效应间无显著性差别,且IL-1β对ATP和ACh诱导的窦神经放电的增高效应也无显著影响。这些结果提示,IL-1β对EAH诱导的窦神经放电无调节作用。     

外源性硫化氢对创伤失血性休克大鼠血浆炎症因子的影响

目的:研究外源性硫化氢(H2S)对创伤失血性休克大鼠炎症反应的影响。方法:选择健康成年雄性SD大鼠随机分为四组:假手术组(Sham),模型组(HTS),生理盐水组(NS),NaHS处理组(NaHS),采用创伤失血性休克模型,Sham组完成所有手术操作,但不放血和复苏,HTS组完成所有手术操作放血后给予Ringer’s液复苏,NS组放血后在Ringer’s液复苏前腹腔注射与NaHS组等容量的生理盐水,NaHS组在复苏前给与NaHS28μmol/kg(生理盐水稀释至0.5ml)腹腔注射。持续监测各组平均动脉压(MAP)及心律(HR),并通过测定血浆中TNF-α、IL-1β、IL-6和IL-10浓度的变化,观察外源性硫化氢对创伤失血性休克大鼠血浆炎症因子的影响。结果:①与HTS组及NS组比较,NaHS组复苏后MAP明显改善(P<0.05)。②与HTS组及NS组比较,复苏后1小时NaHS组血浆TNFα、IL-1β、IL-6浓度明显降低(P<0.05);而IL-10浓度四组间差异不明显(P>0.05)。结论:外源性硫化氢可改善创伤失血性休克大鼠复苏后平均动脉压及抑制复苏后早期炎症反应。     

脊髓水平iNOS在吗啡依赖大鼠戒断反应中的作用

目的:探讨脊髓水平诱导型一氧化氮合酶在吗啡依赖大鼠戒断反应中的作用。方法:健康雄性SD大鼠72只,体重200~250 g,吗啡剂量每次10 mg/kg,每日2次,隔日每次增加10 mg/kg,至第6天末次注射50 mg/kg,大鼠腹腔注射纳洛酮4 mg/kg建立吗啡依赖及戒断模型,在纳洛酮激发戒断前30 min鞘内注射iNOS特异性抑制剂氨基胍(AG)150μg。分为正常对照组、吗啡依赖组、吗啡戒断组、AG组。采用行为学(n=8)、免疫组织化学(n=6)和Western blot(n=4)方法观察鞘内应用iNOS特异性抑制剂氨基胍对吗啡依赖大鼠纳洛酮催促戒断反应和脊髓神经元iNOS表达的影响。结果:AG组戒断症状评分和戒断组促诱发痛评分均低于戒断组(P<0.05)。免疫组织化学和Western blot显示戒断组大鼠脊髓iNOS阳性神经元的数目和蛋白的表达增高,而AG组大鼠脊髓iNOS阳性神经元的数目和iNOS蛋白的表达低于戒断组(P<0.05)。结论:脊髓水平iNOS表达上调可能参与介导吗啡戒断反应。     

Pharmacological preconditioning with resveratrol: role of nitric oxide

Resveratrol (trans-3,4',5-trihydroxystilbene), a recently described grape-derived polyphenolic antioxidant, has been found to protect the heart from ischemic-reperfusion injury. The present study sought to determine the mechanism of cardioprotection by investigating the ability of resveratrol to precondition the heart. Isolated perfused rat hearts were randomly divided into six groups: group I was perfused for 15 min with Kreb-Henseleit buffer (KHB) only; group II was perfused with 10 microM resveratrol; group III was perfused with 10 microM resveratrol plus 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide (NO) synthase (NOS) inhibitor; group IV was perfused with 10 microM resveratrol plus 100 microM aminoguanidine (AG), an inducible NOS (iNOS) blocker; and groups V and VI consisted of hearts perfused with L-NAME and AG, respectively. The perfusion was then switched to working mode, and all hearts were made globally ischemic for 30 min followed by 2 h of reperfusion. Preconditioning of the hearts with resveratrol provided cardioprotection as evidenced by improved postischemic ventricular functional recovery (developed pressure and aortic flow) and reduced myocardial infarct size and cardiomyocyte apoptosis. Resveratrol-mediated cardioprotection was completely abolished by both L-NAME and AG. In a separate study, hearts were examined for iNOS mRNA induction. Resveratrol caused an induction of the expression of iNOS mRNA beginning at 30 min after reperfusion, increasing steadily up to 60 min of reperfusion, and then decreasing progressively up to 2 h after reperfusion. Preperfusion of the hearts with AG almost completely blocked the induction of iNOS. The results of our study demonstrate that resveratrol can pharmacologically precondition the heart in a NO-dependent manner.     

大鼠肢体缺血/再灌注后肺损伤及一氧化氮合酶的变化与意义

目的：研究大鼠肢体缺血／再灌注后急性肺损伤时,内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（i-NOS）的表达及其在急性肺损伤发生中的作用。方法：雄性Wistar大鼠于后肢根部阻断血流后松解（4h／4h）,分别给予L-Arg和氨基胍（AG）预先干预,分为control、IR、L-Arg和AG组,免疫组织化学方法检测肺组织中iNOS和eNOS的表达,同时检测肺组织中MDA、MPO、W／D和NO2^-／NO3^-值,肺组织形态学观察以评价肺损伤的程度。结果：与control组比较,I／R组eNOS表达降低,iNOS表达增强,MDA、MPO、W／D和NO2^-／NO3^-值增加。肺组织充血、炎细胞浸润,肺泡腔渗液;与I／R组比较,L-Arg组eNOS、iNOS表达无明显变化,NO2^-／NO3^-增加。MDA、MPO、W／D降低,肺组织损伤有减轻趋势,AG组eNOS表达无明显变化,iNOS活性降低,NO2^-／NO3^-减少,MDA、MPO、W／D增加,肺组织损伤有加重趋势。结论：肢体缺血／再灌注急性肺损伤过程中,iNOS表达增加,NO生成增多,在肺损伤发生中有一定的保护作用。     

Crocin reduces the inflammation response in rheumatoid arthritis

This study is to determine the role and mechanism of crocin in rheumatoid arthritis (RA). Totally 60 Wistar SD rats were randomly divided into control group, RA model group, methotrexate group, crocin high dose, middle dose, and low dose groups. The paw swelling degree, arthritis score, thymus and spleen index, the mRNA and protein levels of iNOS, and the serum content of TNF-α, IL-1β, and IL-6 were evaluated. Crocin treatment significantly alleviated the paw swelling of RA rats. The arthritis score in crocin treatment groups was significantly lower than that in RA model group. Additionally, the thymus index, but not the spleen index, declined remarkably in crocin treatment groups than in RA model group. Besides, crocin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6. Crocin may exert potent anti-RA effects through inhibiting cytokine.     

硫化氢对1型糖尿病大鼠膈肌NO含量和iNOS活性的影响

目的：观察硫化氢（H2S）对1型糖尿病大鼠膈肌一氧化氮（NO）含量和诱导型一氧化氮合酶（iNOS）活性的影响。方法：将32只雄性SD大鼠随机分为4组：正常组（NC组）、糖尿病组（DM组）、糖尿病治疗组（DM + NaHS组）和NaHS对照组（NaHS组）（n=8）。采用一次性腹腔注射链脲佐菌素55 mg/kg制备1型糖尿病大鼠模型,造模成功后第4周起,DM + NaHS组和NaHS组大鼠腹腔注射NaHS溶液14μmol/kg干预治疗。连续注射5周后,测大鼠空腹血糖值（FBG）和膈肌重量/体重量比（DW/BW）;HE染色观察膈肌显微结构变化;利用NOS分型测试盒测膈肌组织iNOS活性;硝酸还原法测定膈肌组织NO含量;利用RT-PCR和Western blot分别检测膈肌组织iNOS mRNA和蛋白表达。结果：与NC组比较,DM组大鼠FBG显著升高,膈肌显微结构损伤明显,DW/BW下降,膈肌组织iNOS活性和NO含量显著增加,iNOS mRNA和蛋白表达明显增高,NaHS组各项指标差异无统计学意义。与DM组比较,DM + NaHS组膈肌显微结构明显改善,DW/BW增高,膈肌组织iNOS活性和NO含量明显下降,iNOS mRNA和蛋白表达显著降低。结论：外源性补充H2S可能通过下调膈肌组织iNOS活性和蛋白表达,降低NO含量,进而保护糖尿病大鼠膈肌的功能。     

Effect of chronic administration of aminoguanidine on the reactivity of pulmonary vessels in rats with monocrotaline-induced pulmonary hypertension

Monocrotaline (MCT)-induced pulmonary hepertension (PH) is associated with impaired endothelium-dependent relaxation and increased activity of inducible NO-synthase (iNOS). To examine the role of iNOS in MCT-induced PH, we used iNOS inhibitor: aminoguanidine (AG). The PH was simulated with a subcutaneous injection of 60 mg/kg MCT to Wistar rats; control rats were injected with saline. Then each group was separated into 2 subgroups: the 1st one was given drinking water (MCT-C and C-C groups) whereas the 2nd one was given AG in drinking water (15 mg/(kg(-1) x day(-1)) (MCT-AG and C-AG groups). In 4 weeks, the perfusion pressure (PP) responses of isolated pulmonary arteries to acetylcholine (Ach) and activator of soluble guanylate cyclase (sGC), FPTO, were examined. In the MCT-C group, a decrease of relative PP to perfusion of 1 x 10(-8) M and 5 x 10(-8) M Ach and 1 x 10(-8) M FPTO was diminished. This reduction of relaxant responses in MCT-treated rats was prevented by AG treatment. The findings suggest that AG administration restores the impaired endothelium-dependent and sGC-dependent relaxation of the pulmonary artery at MCT-induced PH.     

Immune characteristics study of AG490, a signal pathway inhibitor,in EAE model mice

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS). Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh) secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC) through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases. In the present study, the experimental mice were divided into 3 groups, vehicle group and AG490 group were given MOG35-55 to induce EAE model, from the third day after immunization, the mice were given vehicle or AG490 by intraperitoneal injection every other day. All mice were assessed clinical scores after immunization. On twentieth day, all mice were sacrificed, HE staining and solochrome cyanine staining were performed to evaluate inflammatory cells infiltration and demyelination, spleen sections were stained with PNA-FITC to analyze the difference in germinal center. Compared with vehicle group, the incidence of AG490 group was deceased, onset time was delayed, the severity was significantly reduced. The inflammatory cells and demyelination in AG490 group were lower than those in vehicle group. Immunofluorescence showed the fluorescence intensity of AG490 group was significantly lower than in the vehicle group, but higher than that of control group.     

Inhibitory effect of inducible nitric oxide synthase inhibitors on DMBA-induced hamster buccal–pouch squamous-cell carcinogenesis

We investigated the effects of two NOS inhibitors (AG and l-NAME) on DMBA-induced hamster buccal-pouch carcinogenesis. Six hundred Syrian golden hamsters were split into two divisions (I and II); divisions split into three groups (experimental groups A and B, control group C); and each group into subgroups of 20 (A1-A6, B1-B6 and C1-C3). The pouches of animals in groups A1-A3 were painted first with AG of differing concentrations (10, 20, and 30 micromol/ml) and then 30 min later with DMBA (0.5%), thrice weekly for 9 weeks. Subgroups A4-A6 only received AG treatment. Groups B1 to B6 were similarly treated with l-NAME. Animals in division II were treated in the same manner for 13 weeks. Post-mortem analysis revealed that both inhibitors can suppress the development of epithelial dysplasias and squamous-cell carcinomas. An associated increase in the numbers of epithelial hyperplasias was paralleled by a decrease in iNOS protein expression. This animal model can be employed to evaluate the potential use of iNOS inhibitors as novel therapeutic tools for oral squamous-cell carcinogenesis.     

Immunoregulatory role of nitric oxide in Kilham rat virus-induced autoimmune diabetes in DR-BB rats

Macrophages play a critical role in the pathogenesis of Kilham rat virus (KRV)-induced autoimmune diabetes in diabetes-resistant BioBreeding (DR-BB) rats. This investigation was initiated to determine the role of macrophage-derived soluble mediators, particularly NO, in the pathogenesis of KRV-induced diabetes in DR-BB rats. We found that the expression of inducible NO synthase (iNOS), an enzyme responsible for NO production, was significantly increased during the early phase of KRV infection. Inhibition of iNOS by aminoguanidine (AG) treatment resulted in the prevention of diabetes in KRV-infected animals. The expression of IL-1beta, TNF-alpha, and IL-12 was significantly decreased in the spleen of AG-treated, KRV-infected DR-BB rats compared with PBS-treated, KRV-infected control rats. Subsequent experiments revealed that AG treatment exerted its preventive effect in KRV-infected rats by maintaining the finely tuned immune balance normally disrupted by KRV, evidenced by a significant decrease in the expression of IFN-gamma, but not IL-4, and a decrease in Th1-type chemokine receptors CCR5, CXCR3, and CXCR4. We also found that iNOS inhibition by AG decreased the KRV-induced expression of MHC class II molecules and IL-2R alpha-chain, resulting in the suppression of T cell activation, evidenced by the decreased cytolytic activity of CD8(+) T cells. We conclude that NO plays a critical immunoregulatory role by up-regulating macrophage-derived proinflammatory cytokines, up-regulating the Th1 immune response, and activating T cells, leading to type 1 diabetes after KRV infection, whereas suppression of NO production by AG treatment prevents KRV-induced autoimmune diabetes in DR-BB rats.     

脊髓水平nNOS和iNOS在吗啡戒断反应中的作用差异

目的:观察鞘内注射选择性一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)抑制剂对吗啡依赖大鼠纳洛酮催促戒断反应、脊髓Fos蛋白表达和脊髓神经元nNOS和iNOS表达的影响,以探讨nNOS和iNOS在吗啡依赖和戒断反应中的作用。方法:在大鼠吗啡依赖和戒断模型上,采用行为学、免疫组织化学和Western blot方法观察鞘内应用nNOS抑制剂7-硝基吲哚(7-Ni)和iNOS抑制剂氨基胍(AG)对吗啡依赖大鼠纳洛酮催促戒断反应、脊髓Fos蛋白表达和脊髓神经元nNOS和iNOS表达的影响。结果:①鞘内注射7-Ni、AG可明显减轻吗啡依赖大鼠戒断症状,戒断组戒断症状评分为28.6±4.89,7-Ni组为16.2±3.99(P<0.01),AG组为22.94±4.0(P<0.05);戒断组TEA评分为13.5±2.55,7-Ni、AG组分别为7.5±2.56、10.5±2.71(P<0.05);②鞘内注射7-Ni、AG可减少脊髓背角Fos阳性神经元的数目,7-Ni、AG组为228.2±49.5、296.8±50.6,低于戒断组(380±71,P<0.05);③7-Ni、AG组nNOS和iNOS阳性神经元的数目分别为169±32、10.2±2.85,均低于戒断组(239±45,16.8±5.1,P<0.05),两给药组脊髓NOS蛋白的表达也显著减少。结论:nNOS和iNOS抑制剂能减轻吗啡依赖及戒断大鼠的戒断症状和在脊髓水平抑制nNOS和iNOS的表达,nNOS起主要作用而iNOS可能起辅助作用。