Are common mutations of cystathionine β-synthase involved in the aetiology of neural tube defects?

Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hcy are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine β-synthase (CBS), which is one of the main enzymes that controls Hcy levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland.     

Ultrastructural distribution of NADPH-diaphorase in the normal hippocampus and after long-term potentiation

Summary The distribution of the enzyme nitric oxide synthase (NOS) was investigated at the ultrastructural level in synaptic structures of the hippocampal formation in relation to long-term potentiation (LTP), based on the histochemical NADPH-diaphorase (NADPH-d) staining with the tetrazolium salt BSPT. BSPT-formazan, the osmiophilic reaction product, was found to be selectively distributed and predominantly attached to membranes of the endoplasmic reticulum. In synaptic regions mainly the presynaptic sides showed labeling. Although several groups have demonstrated a principal involvement of NO in the LTP-mechanism, we found only a low, statistically insignificant increase in NADPH-d stained presynaptic areas of the dentate gyrus, where LTP was evoked. Postsynaptic elements also did not show any noticeable differences. Based on the present results, the predominantly presynaptic localization of NOS should be preferably considered in models describing a functional role of NO in LTP formation, despite the fact that we failed to reveal any indications for an LTP-related change in synaptically located NADPH-d.     

人参总皂甙对不完全性脑缺血后海马CA1区NOS阳性神经元表达的影响

目的探讨人参总皂甙(GS)对不完全性脑缺血及再灌注不同时间后海马CA1区一氧化氮合酶(NOS)的影响及对神经元的保护作用.方法用双侧颈总动脉夹闭加放血的方法制成大鼠不完性脑缺血及再灌注模型,以还原烟酰胺腺嘌呤二核苷酸脱氢酶(NADPH-d)组织化学方法观察缺血及再灌注后海马CA1区NOS阳性神经元变化及GS对其的影响.结果单纯缺血组海马CA1区在缺血30min时NOS阳性细胞数最高(44.5±7.42),为假手术组2倍,再灌注2h、12h、24h、3d后逐渐下降,5d时恢复正常水平(21.12±3.50),缺血再灌注3d、5d时出现神经细胞损伤.GS能抑制缺血30min及再灌注各时程中NOS阳性神经元数量变化,并能预防缺血再灌注后迟发的神经元损害.结论GS对大鼠不完全性脑缺血及再灌注不同时程后海马CA1区NOS的异常表达有抑制作用,对神经元的保护作用.     

NO在体外循环中脑损伤作用机制的研究进展

一氧化氮及一氧化氮合酶在体外循环导致的脑损伤中具有重要作用,它可以通过扩张血管/抑制血小板聚集与黏附/减少细胞凋亡等对脑组织产生保护作用。一氧化氮的临床应用仍需对其作用机制作进一步深入研究。     

异丙酚对慢性神经痛大鼠脊髓诱导型一氧化氮合酶表达的影响

目的 研究不同剂量异丙酚对慢性神经痛大鼠触诱发痛痛阈及其脊髓组织诱导型一氧化氮合酶(iNOS)mRNA的影响。方法 Wistar大鼠40只,随机分为四组,Ⅰ组为空白对照;Ⅱ、Ⅲ、Ⅳ组结扎左侧坐骨神经。术后第7天,Ⅰ、Ⅱ组腹腔注射生理盐水50 ml·kg-1,Ⅲ、Ⅳ组腹腔注射异丙酚50 ml·kg-1或75ml·kg-1,每天一次共6 d。在术后第6、10和12天,使用Von Frey法分别测定各组大鼠触诱发痛痛阈,比较不同剂量的异丙酚对大鼠痛阈的影响。术后第12天取L4-5和L5-6节段脊神经节和脊髓组织,采用半定量RT-PCR法,对各组大鼠脊髓组织iNOS mRNA表达进行检测。结果 术后第10和12天,Ⅲ、Ⅳ组大鼠双侧的痛阈值高于Ⅱ组(P<0.05);术后第12天,Ⅲ、Ⅳ组大鼠脊髓组织iNOS mRNA表达低于Ⅱ组(P<0.05)。结论 异丙酚通过抑制脊髓组织iNOS mRNA转录,降低其表达,而起到一定的抗伤害作用。     

实验性糖尿病早期大鼠背根神经节一氧化氮合酶基因表达的变化

目的：观察糖尿病早期(2周)大鼠背根神经节(DRG)中一氧化氮合酶(nNOS、iNOS、eNOS)的表达变化以及胰岛素对其的影响。方法：按60mg／kg一次性腹腔注射链脲佐菌素(STZ)制备胰岛素依赖性糖尿病大鼠模型(16只)，造模成功后随机分成2组(模型组和治疗组)，治疗组于造模成功后第2天开始给予胰岛素治疗，正常对照组(8只)与模型组予皮下注射同样体积的生理盐水。2周后取各组大鼠背根神经节，Trizol法提取总RNA，应用RT—PCR法测定3种NOS mRNA的表达。结果：在糖尿病早期大鼠DRG中，iNOS表达明显上调，胰岛素能有效逆转此变化。而nNOS和eNOS的表达无明显变化。结论：在早期糖尿病DRG中iNOS基因表达异常，可能与糖尿病外周神经病变的发生发展有关。     

猪心脏移植缺血再灌注损伤中NO和NOS的表达

①目的　了解猪同种原位心脏移植术后早期一氧化氮 (NO)、一氧化氮合酶 (NOS)含量的变化 ,及其与早期缺血再灌注损伤的关系。②方法　建立猪同种原位心脏移植模型。供心在移植前低温保存 (Thomas液 ,4℃ ) 4h ,移植成功心脏复搏后 2h取材。应用组织化学方法测定心肌组织中NO、NOS的含量 ,应用核酸原位末端标记法 (TUNEL)测定心肌细胞凋亡指数 ,作为评价心肌缺血再灌注损伤的指标。以正常心肌及单纯缺血心肌组织作为对照。③结果　移植后心肌组织NO、NOS的含量较缺血组与正常组低 ,差异有显著意义 (F =2 7.2 2 9、16 .2 0 3,q =5 .716～ 6 .4 12 ,P <0 .0 1)。移植组心肌细胞凋亡指数与正常组及缺血组比较明显升高 ,差异有显著性(F =16 3.884 ,q =7.4 82、6 .975 ,P <0 .0 1)。心肌组织NO、NOS含量与心肌细胞凋亡指数呈负相关关系 (r =- 0 .886、- 0 .795 ,P <0 .0 1)。④结论　猪心脏移植后早期心肌缺血再灌注损伤所致的细胞死亡主要表现为心肌细胞凋亡 ;再灌注期间内源性NO、NOS的减少参与了心脏移植后早期缺血再灌注损伤的发生     

Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

Hypoxiaisadirectfactorcausinghypoxicpul monaryhypertension (HPH) .hypoxiainduciblefac tor 1α (HIF 1α)isfoundtobethemostcrucialfactorsofarwhichmediatesthecellularresponsetohypoxi a[1] .OurpreviousstudyrevealedthatoverexpressionofHIF 1andendothelin 1(ET 1…     

新生大鼠缺氧缺血性脑损伤后血清和脑组织NO、NOS变化的相关性

目的 研究缺氧缺血性脑损伤(HIBD)后血清和脑组织中NO、NOS的变化，探讨其是否存在相关性。方法 取空白对照组、假手术组、缺氧缺血后30min、2h、24h、72h大鼠血清、脑组织标本进行NO和NOS的检测。NO测定采用硝酸还原酶法，用分光光度计比色法测定NO和NOS。结果 (1)缺氧缺血组NO、NOS增高，与假手术组、空白对照组比较差异有显著性，但后两组差异无显著性。(2)新生大鼠脑缺氧缺血后NO、NOS随时间的延长而逐渐升高。(3)血清、脑组织NO、NOS的变化存在相关性。结论 新生大鼠缺氧缺血性脑损伤后血清和脑组织中NO、NOS都有不同程度的升高，而且存在相关性。可以通过血NO、NOS的检测了解脑组织的受损情况。