胱硫醚β-合成酶T833C基因多态性与原发性高血压关系的Meta分析

目的：探讨胱硫醚β-合成酶（CBS）T833C基因多态性与原发性高血压（EH）的相关性。方法计算机检索万方数据知识服务平台、中国知网、维普资讯、Embase数据库及 PubMed,收集有关中国人CBS T833C基因多态性与EH的病例－对照研究。由两名研究员独立评价纳入文献的质量,提取有效数据,采用RevMan 5．2软件进行Meta分析。结果共纳入5个研究CBS T833C基因多态性与EH关系的病例－对照研究,其中病例组1747例,对照组1698例。 Meta分析结果显示,CBS基因T833位点C突变与EH发病风险正相关（OR＝1．90,95％CI：1．02～3．53,P＜0．05）。结论 CBS 基因T833位点C突变与EH发病风险正相关。     

CBS基因甲基化对叶酸干预HHcy效果的性别特异性研究

目的 探究胱硫醚β合成酶(CBS)基因启动子甲基化在不同性别中对叶酸干预高同型半胱氨酸血症(HHcy)效果的影响。 方法 研究对象选自郑州大学第五附属医院住院的1 071例HHcy患者，进行90天的口服叶酸(5 mg/d)干预治疗。根据治疗后复查的血浆同型半胱氨酸(Hcy)水平将患者分为未达标组(Hcy≥15 μmol/L)和达标组(Hcy<15 μmol/L)。运用MethylTargetTM目标区域甲基化测序法检测299例患者CBS基因甲基化水平。运用多因素logistic回归分析CBS基因甲基化在不同性别中对叶酸干预HHcy效果的影响。运用受试者工作特征曲线(ROC)分析CBS基因甲基化在不同性别中对HHcy疗效的预测效果。 结果 CBS基因甲基化水平在两组间的分布差异仅在男性中有统计学意义( t =2.428， P =0.016)。较低水平的CBS基因甲基化在男性中能显著增加叶酸干预HHcy未达标的风险( OR =2.63, 95% CI : 1.41~4.92)。男性患者中CBS基因甲基化与HHcy疗效的ROC曲线下的面积为0.60 (95% CI : 0.52~0.68)。在女性患者中，基因甲基化与HHcy疗效的关联无统计学意义( OR =1.09，95% CI : 0.50~2.37)。 结论 CBS启动子甲基化对叶酸干预HHcy效果的影响存在性别特异性。     

氨基氧乙酸对大鼠局灶性脑缺血损伤的影响

目的 评价氨基氧乙酸对大鼠局灶性脑缺血损伤的影响.方法 健康雄性SD大鼠80只,体重250～280 g,月龄2.5个月,采用随机数字表法,将其随机分为5组(n＝16):假手术组(S组)、脑缺血组(Ⅰ组)、低、中、高剂量氨基氧乙酸组(AL组、AM组和AH组).Ⅰ组、AL组、AM组和AH组采用线栓法(阻塞大脑中动脉)制备大鼠局灶性脑缺血损伤模型.AL组、AM组和AH组于缺血3h时分别腹腔注射氨基氧乙酸25、50、100 μmol/kg,S组和Ⅰ组给予等容量生理盐水1ml/kg.每组于给予氨基氧乙酸后21 h时取8只大鼠,进行神经功能缺陷评分,然后处死大鼠,取脑组织,分离皮层、海马、纹状体,测定胱硫醚-β合酶( CBS)活性.每组于给予氨基氧乙酸后21 h时处死另外8只大鼠,取脑组织,测定脑梗死体积.结果 与S组比较,Ⅰ组神经功能缺陷评分、皮层和海马CBS活性升高,脑梗死体积扩大(P<0.05),纹状体CBS活性差异无统计学意义(P＞0.05);与Ⅰ组比较,AM组和AH组神经功能缺陷评分、皮层和海马CBS活性降低,脑梗死体积缩小,纹状体CBS活性差异无统计学意义(P＞0.05);AL组上述指标差异无统计学意义(P＞0.05).结论 氨基氧乙酸可减轻大鼠局灶性脑缺血损伤,其机制与抑制CBS活性,减少H2S生成有关.     

Cystathionine gamma-lyase-deficient smooth muscle cells exhibit redox imbalance and apoptosis under hypoxic stress conditions

BACKGROUND:

Hydrogen sulphide (H₂S) has recently emerged as a novel and important gasotransmitter in the cardiovascular system, where it is generated mainly by cystathionine gamma-lyase (CSE). Abnormal metabolism and functions of the CSE/H₂S pathway have been linked to various cardiovascular diseases including atherosclerosis and hypertension. An important role for H₂S in regulating the balance between cellular growth and death has been demonstrated whereby inhibition of the endogenous CSE/H₂S pathway results in greater apoptosis of vascular smooth muscle cells (SMCs). H₂S is increasingly recognized as a critical regulator of vascular integrity, but its role in SMCs during hypoxia has not been explored in a model of CSE deficiency.

METHODS:

Cell viability, apoptosis, redox status and mitochondrial activity in hypoxia-exposed (12 h at 1% O₂) SMCs derived from the mesenteric artery of CSE-knockout (CSE-KO) mice were analyzed. These were compared with those from CSE-wild-type (CSE-WT) mice.

RESULTS:

CSE-KO cells exhibited redox imbalance and aberrant mitochondrial activity versus CSE-WT cells, indicating an essential regulatory role for the endogenous CSE/H₂S pathway on SMC function. CSE-KO cells were also more susceptible to hypoxia-induced cell death, indicating a critical contribution of endogenous CSE/H₂S pathway to the protective hypoxia stress response.

CONCLUSION:

These findings support the concept that H₂S is a crucial regulator of vascular homeostasis, the deficiency of which is associated with various pathologies, and provide further evidence that H₂S is a potent vasculoprotectant.     

Production of endogenous hydrogen sulfide in human gingival tissue

ObjectiveEndogenous hydrogen sulfide (H₂S) has recently been shown to play an important role in inflammation, but the role of endogenous H₂S in the human gingival tissue is unknown. The aim of this study was to investigate whether gingiva had enzymes for H₂S synthesis, and whether the effect of these enzymes for H₂S production changed with periodontal inflammation.DesignGingival tissues were collected from patients undergoing periodontal operation including gingivitis, moderate chronic periodontitis, severe chronic periodontitis and normal controls. RT-PCR and western blotting were performed to measure mRNA and protein levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) for H₂S production. Immunohistochemistry was carried out to detect the location of the enzymes. H₂S levels and synthesis in gingival tissue were evaluated with modified methylene blue method.ResultsThe mRNA and protein of CBS and CSE were both expressed in human gingiva and raised significantly in moderate and severe periodontitis compared of that in healthy control. CBS, but not CSE, increased in gingivitis (p < 0.05). However, there was no significant difference of H₂S level and synthesis among these groups (p > 0.05).ConclusionsBoth CBS and CSE were expressed in human gingival tissue. The mRNA and protein levels of CBS and CSE were up-regulated in periodontitis.     

胱硫醚-β-合成酶基因突变与有家族聚集现象脑血管病关系探讨

目的:探讨胱硫醚-β-合成酶(CBS)基因突变与有家族聚集现象脑血管病的关系,从而探讨不同群体对脑血管病的易感性的差异。方法:采用聚合酶链式反应-单链构象多态性分析法(PCR—SSCP)分析25个有家族聚集现象的脑血管病家系成员CBS基因C699T、C1080T突变;扩增阻滞突变系统分析法(AMRS)分析CBS基因T833C突变。结果:①、脑血管病组(包括有家族聚集现象的脑血管病组)的CBS基因C699T突变频率均高于对照组。②、有家族聚集现象的脑血管病组的CBS基因T833C突变频率较散发性脑血管病组有增高的趋势,有家族聚集现象的脑梗死组中患者和Ⅰ级亲属的CBS基因T833C突变频率高于Ⅱ、Ⅲ级亲属;脑血管病组(包括有家族聚集现象的脑血管病组)的CBS基因T833C突变频率均高于对照组。③、有家族聚集现象的脑血管病组的CBS基因C1080T突变频率高于散发性脑血管病组,有家族聚集现象的脑血管病组中患者和Ⅰ级亲属的CBS基因C1080T突变频率高于Ⅱ＼Ⅲ级亲属;脑血管病组(包括有家族聚集现象的脑血管病组)的CBS基因C1080T突变频率均高于对照组。结论:有家族聚集现象的脑血管病可能与CBSC699T、CBSC1080T、CBST833C基因突变有关。     

门静脉高压大鼠内源性硫化氢体系的变化

在肝硬化门静脉高压形成中，门静脉系统的血流量增加是门静脉高压产生和加重的重要因素之一，近几年来人们发现气体信号分子NO、CO可以引起内脏血管扩张而使门静脉系统血流量增加。最近的研究发现H2S具有与NO、CO相似的生物学效应，如舒张血管、抑制平滑肌细胞增殖等。内源性H2S在诸多心血管疾病的发病过程中发挥着重要的病理生理学作用，广泛参与低氧性肺动脉高压、肺动脉高压、高血压、感染性休克等心肺疾病的发病过程。在门静脉高压的发病过程中是否也有H2S的参与，目前国内外鲜见报道。本研究以部分门静脉结扎大鼠为对象，观察门静脉高压大鼠门静脉压力的变化以及CSE基因表达的改变，以探讨H2S在门静脉高压中的作用。     

胱硫醚β合酶基因T833C突变与脑梗死发生的相关性研究

目的探讨脑梗死患者同型半胱氨酸(Hcy)代谢相关酶胱硫醚β合酶(CBS)基因T833C位碱基突变与脑梗死发病的相关性。方法对67例经头部CT或MR I证实为脑梗死的患者(脑梗死组)和31名健康对照者(对照组),应用聚合酶链反应(PCR)扩增法检测CBS基因T833C多态性,采用高效液相色谱法测定血清Hcy水平。结果在脑梗死组有9例CBS基因纯合子突变,28例为杂合子突变;对照组3名为纯合子突变,5名为杂合子突变。两组基因型频率分布差异亦有显著意义,2χ=11.429,P<0.01;脑梗死组C等位基因频率为34.33%,T等位基因频率为65.67%,与对照组比较差异有显著意义,2χ=8.978,P<0.01。CBS基因杂合突变者血清Hcy浓度显著高于正常基因者(t=4.612,P<0.01)。脑梗死组患者血清Hcy浓度为(23±7)nmol/m l,显著高于对照组(13±4)nmol/m l,两组比较差异有显著性(t=8.826,P<0.01)。结论Hcy血症是脑梗死的独立危险因素,而CBS基因T833C点突变可能是其发病的重要遗传因素。     

Homocystinuria: Challenges in diagnosis and management

Two patients with homocystinuria are discussed. Both patients presented with behavioural abnormalities and deficits in attention – symptoms that are frequently encountered in paediatric office practice. In both cases, the diagnosis of homocystinuria was not made at initial presentation. Subtle but definite phenotypic features eventually provided the first indication of homocystinuria between the ages of five to seven years. Laboratory screening confirmed homocystine in the urine, and elevated methionine and homocysteine plasma levels in both patients. Patients with inborn errors of metabolism such as homocystinuria are treated first by family physicians and paediatricians. Without a high index of suspicion, physicians can easily overlook a diagnosis of homocystinuria. The management of patients with homocystinuria continues to pose a challenge to physicians and care givers.