绝经后骨质疏松症相关基因的研究进展

绝经后骨质疏松症是困扰绝经后妇女的常见病,基因因素在其发病过程中占有很大比例,近几年已成为研究热点,本就其几种相关基因的研究进展做一概述,以期进一步对其发病机制进行探索。     

绝经后骨质疏松症相关基因的研究进展

绝经后骨质疏松症是困扰绝经后妇女的常见病 ,基因因素在其发病过程中占有很大比例 ,近几年已成为研究热点。本文就其几种相关基因的研究进展做一概述 ,以期进一步对其发病机制进行探索     

绝经后骨质疏松症患者血清NO-iNOS系统及相关激素水平变化的探讨

观察绝经后骨质疏松症(PMO)患者NO、诱导型一氧化氮合酶(iNOS)及E2、GH、PTH、25(OH)D3等相关激素,探讨NO-iNOS系统及相关激素在骨质疏松发病机制中的作用和意义.80例绝经1年以上女性,根据扫描骨密度(BMD),Tscore值,分为骨质疏松组(OP组)34例,非骨质疏松组(NOP组)46例,及绝...     

以患者为中心的系统化健康教育在围绝经期及绝经后骨质疏松症患者中的运用

目的:探讨以患者为中心的系统化健康教育对围绝经期及绝经后骨质疏松症(osteoporosis,OP)患者骨质疏松知识、自我效能及骨密度的影响.方法:将156名围绝经期及绝经后OP患者按照计算机产生的随机数字分为观察组和对照组,对照组实施常规的健康教育,观察组以患者为中心的系统化健康教育方案,收集并比较两组在干预前及干预6个月后的骨质疏松知识(osteoporosisknowledge tests,OKT)、骨质疏松自我效能(osteoporosis self-efficacy scale,OSES)及骨密度的变化情况.结果:干预后两组在骨质疏松知识总分及各维度得分、骨质疏松自我效能总分及各维度得分、L1～L4及左股骨的骨密度均较干预前明显提升,且观察组在上述各项目的数值均明显高于对照组,差异具有统计学意义(P＜0.05).结论:实施以患者为中心的系统化健康教育可明显提升围绝经期及绝经后OP患者对疾病的认识水平、应对疾病的自我效能以及骨密度水平,对于预防骨折及改善生命质量具有积极的促进意义.     

绝经后骨质疏松症患者细胞因子、骨密度及雌激素水平的关系

绝经后骨质疏松症是指绝经后妇女由于体内卵巢功能低下,雌激素水平低落,骨偶联过程失调,破骨细胞的骨吸收大于成骨细胞的骨形成作用所导致的骨量减少,骨脆性增加,进而易于发生骨折的代谢性骨疾病。雌激素水平降低是绝经后骨质疏松发病的首要原因,本文旨在观察绝经后骨质疏松症（PMOP）的雌激素水平与细胞因子的关系。     

凋亡及免疫激活相关基因在先兆子痫胎盘中的表达

目的：探讨细胞凋亡相关基因在先兆子痫胎盘组织中的表达谱及其影响机制。方法：采用分别包含220余种人类细胞因子相关基因或人类环境激素相关基因cDNA片段的基因芯片，检测严格配伍的先兆子痫和正常胎盘组织中基因表达谱的差异。结果：先兆子痫胎盘中与细胞增殖周期调控及凋亡相关的多种基因表达发生了变化，且大多数呈现表达增强。此外，与免疫系统激活有关的多条基因在先兆子痫胎盘中的表达也比正常胎盘高。结论：胎盘组织中多种与细胞凋亡调节有关的基因表达异常与先兆子痫的病理发生有关，而免疫系统激活也可能是其原因之一。     

雌激素受体-β基因多态性及山茶籽油与广西壮族绝经后骨质疏松症的关联性

目的:探索雌激素受体-β(ER--β)基因多态性及山茶籽油与广西壮族妇女绝经后骨质疏松症(PMOP)的关联性。方法:590例广西长期食用山茶籽油壮族妇女和600例广西长期非食用山茶籽油壮族妇女,定量超声骨质密度仪检测2组右侧足跟骨测量宽带超声衰减值(βUA),PCR-RFLP检测2组ER-β基因多态性。结果:同一年龄组相比较,食用山茶籽油组绝经妇女骨质疏松症的患病率明显低于非食用山茶籽油组绝经妇女。ER--β基因RsaⅠ等位基因频率在2组中存在着显著性差异,r等位基因患PMOP的风险是R等位基因的1.442倍(OR=1.442,95%CI为1.215~1.711)。食用山茶籽油组绝经后骨质疏松症组携带AluⅠ酶切位点的a等位基因分布频率明显少于非食用山茶籽油组绝经后骨质疏松症组。结论:提示ER-βRsaⅠ酶切位点的r等位基因可能是PMOP的遗传易感基因;食用山茶籽油对PMOP有防治作用,AluⅠ酶切位点的a等位基因是对山茶籽油起交互作用的敏感基因。     

绝经后骨质疏松症病人I型胶原的变化

目的 研究I型胶原合成及代谢在绝经后骨质疏松症发病中的作用。方法 以绝经后骨质疏松性骨折病人股骨头置换术弃去的股骨头为样本；采用苦味酸天狼星红一偏振光及I型胶原和基质金属蛋白酶-1(MMP—1)抗体免疫组织化学染色，从蛋白水平观察骨中I型胶原的分布和量的变化；地高辛标记的I型胶原和MMP-1cDNA基因探针进行原位杂交，从mRNA水平观察I型胶原和MMP-1的分布和量的变化；从骨中提取I型胶原测定肽链的羟基化水平，观察I型胶原羟基化程度的改变。结果 绝经后骨质疏松性骨折病人胶原含量降低，I型胶原蛋白纤维变细、断裂，结构紊乱。而细胞内I型胶原和MMP—lmRNA以及MMP—1蛋白水平均升高。I型胶原蛋白赖氨酸羟基化程度升高而脯氨酸羟基化程度不变。结论 I型胶原合成及代谢在质和量上的改变在绝经后骨质疏松症发病中起重要作用。     

绝经后骨质疏松症I型胶原代谢的变化

目的 研究I型胶原及其代谢在绝经后骨质疏松症发病中的作用。方法 双侧卵巢切除制造大鼠骨质疏松模型（OVX大鼠）；比色法测定骨中羟脯氨酸浓度，计算胶原含量；苦味酸天狼星红染色，从蛋白水平观察骨中I型胶原的分布和变化；地高辛标记的I型胶原和基质金属蛋白酶－1（MMP－1）基因探针进行原位杂交，从mRNA水平观察I型胶原和MMP－1的分布和变化。结果 OVX大鼠骨中无机盐和胶原含量均降低，I型胶原蛋白纤维变细、断裂、结构紊乱。I型胶原和MMP－1 mRNA水平均升高。结论 I型胶原合成及代谢的改变在绝经后骨质疏松发病中起重要作用。     

Expression profiles of 10 circadian clock genes in human peripheral blood mononuclear cells

The circadian clock system regulates daily rhythms of physiology and behavior. The mammalian master clock in the suprachiasmatic nuclei orchestrates these biological rhythms in peripheral tissues. Since blood is the most accessible tissue source, we sought to dissect the human circadian clock system by characterizing clock gene expression in human peripheral blood mononuclear cells (PBMCs) isolated from eight young, healthy subjects. By evaluating the temporal expression profiles of 10 circadian clock genes, we found that Period 1 (Per1), Per2, and Per3 are rhythmically expressed in human blood samples. Our results suggest that evaluating the rhythmic expression of human Per genes could reveal an individual's circadian phenotype.     

Production of anti-basement membrane-zone antibody by peripheral blood leukocytes of bullous pemphigoid patients

Peripheral blood leukocytes (PBL) from patients with bullous pemphigoid stimulated by pokeweed mitogen (PWM) produce an anti-basement membrane-zone (BMZ) antibody. The antibody producedin vitro was biosynthetically radiolabeled, and its binding to the BMZ was histologically demonstrated by autoradiography. The IgG nature of the antibody was evidenced by the fact that it was absorbed by rabbit anti-human IgG antiserum immunoabsorbents. The peak antibody productionin vitro occurred after 6 days of culture. Antibody producedin vitro did not bind to the BMZ of human skin, but it did bind to the BMZ of the monkey esophagus. Normal human volunteers and control patients did not produce such an antibody. In other experiments the effects of adding serum containing anti-BMZ antibody to the synthesis of Ig by cells of patients and normal subjects were studied. Although serum from patients with bullous pemphigoid stimulated Ig production with either normal or BP-patient PBL, the difference was not statistically significant. The availability of the assay system allows for studying the immunoregulatory mechanism of autoantibody production in bullous pemphigoid.     

SD大鼠绝经后骨质疏松疾病动物模型的构建

目的构建绝经后骨质疏松疾病动物模型,探讨该疾病的发病机制与防治措施。方法将3个月龄健康雌性SD大鼠40只,随机分为2组,分别为去卵巢组和假手术组。去卵巢组切除大鼠双侧卵巢,手术后3个月通过检测体重、阴道涂片、血钙、子宫湿重、骨组织病理学、骨组织形态计量参数等对模型进行评价。结果手术后3个月,去卵巢组大鼠体重较假手术组明显增加(P0.05),子宫湿重、血钙含量较假手术组量明显下降(P0.05),阴道涂片显示去卵巢组大鼠均无发情表现,骨组织病理学观察显示去卵巢大鼠胫骨骨小梁断裂,小梁间距变宽,结构紊乱,骨形态计量学数据显示去卵巢大鼠胫骨、股骨干骺端骨小梁面积百分率、骨小梁平均厚度均较假手术组减少(P0.05)。结论 3个月龄SD大鼠去卵巢后3个月可成功复制出绝经后骨质疏松模型。     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis

Purpose: The aim of this meta-analysis was to assess the safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density (BMD). Methods: Safety of denosumab was compared with placebo or bisphosphonates. A systematic literature search without language restriction was conducted up to January, 2014. The RevMan 5.1 software was used for statistical analysis. Results: A total of 11 English literatures were eventually identified. The pooled data in the overall analysis revealed that there was no significant difference when compared denosumab with placebo or bisphosphonates in any adverse events (AAE) (RR=0.99, 95% CI=0.98-1.01, p=0.29), serious adverse event (SAE) (RR=1.05, 95% CI=0.98-1.13, p=0.18), neoplasm/cancer (RR=1.14, 95% CI=0.95-1.37, p=0.16) and deaths (RR=0.77, 95% CI=0.57-1.04, p=0.09). However, significant differences were found when compared denosumab with placebo or bisphosphonates in SAE related to infection (RR=1.23, 95% CI=1.00-1.52, p=0.05) and non-vertebral fracture (RR=0.86, 95% CI=0.74-1.00, p=0.05). Subgroup analysis was performed by the type of drugs which was used in the control group. The results of subgroup analysis did not demonstrate the differences between denosumab and bisphosphonates in SAE related to infection (RR=1.13, 95% CI=0.63-2.03) and non-vertebral fracture (RR=1.31, 95% CI=0.87-1.98). Conclusions: Compared to placebo, denosumab treatment significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to infection in the postmenopausal women with osteoporosis or low BMD. However, no difference between the safety of denosumab and bisphosphonates was found.     

Expression analysis of psychological stress-associated genes in peripheral blood leukocytes

In this study, we have developed a microarray including 1467 cDNAs that were selected to specifically measure stress response in peripheral blood leukocytes. Venous blood was collected from 10 graduate students 2 h before and 2 or 24 h after an open presentation for their Ph.D. The mRNA levels in leukocytes were compared with those prepared 4 weeks before the presentation. Hierarchical cluster showed that distinct groups of genes uniformly changed their expression values in response to the stress. Bayesian t test identified significantly up-regulated 49 genes and down-regulated 21 genes. Most of them are categorized into cytokines, cytokine receptors, growth- or apoptosis-related molecules, and heat shock proteins, suggesting that stressful life events trigger acute responses in leukocytes. Our results suggest that gene expression profile in peripheral blood leukocytes may be a potentially useful method for the assessment of complex stress responses.     

Virological analysis and phenotypic characterization of peripheral blood lymphocytes of hepatitis C virus-infected patients with and without mixed cryoglobulinaemia

In clinical and pathological terms hepatitis C virus (HCV)-infected patients can be subdivided into two main groups with and without mixed cryoglobulinaemia (MC). Involvement of blood mononuclear cells by HCV has potentially important implications. To this end, HCV-RNA levels in peripheral blood lymphocytes (PBL) preparations of 20 chronically HCV-infected patients with MC were measured and compared with those found in a group of 20 patients without MC matched for age, serum HCV-RNA, infectious genotype, source and presumable duration of infection. Phenotypic abnormalities of PBL subsets in each group of patients were determined by cell surface marker expression and compared. Results showed a significant enrichment of HCV-RNA in PBL of MC patients compared with a non-MC group (P = 0.01). Different distribution of HCV-RNA was accompanied by evidence of an increased frequency of circulating B cells. These data indicate that MC patients are characterized distinctly by a higher quota of cell-associated viral load.