绝经后妇女骨代谢过程中血清基质金属蛋白酶3和骨桥蛋白的变化

背景：骨桥蛋白和基质金属蛋白酶3具有高度的亲和力,此二者的表达可能与骨代谢有关。 目的：观察绝经后妇女血清基质金属蛋白酶3和骨桥蛋白水平,并观察其与骨保护蛋白、骨保护蛋白配体及骨代谢指标的关系。 方法：将120名绝经后妇女分为骨密度正常组、低骨量组和骨质疏松组3 组,对其血清基质金属蛋白酶3、骨桥蛋白、骨保护蛋白、骨保护蛋白配体及骨碱性磷酸酶、骨钙素、Ⅰ型胶原交联C端肽和尿Ⅰ型胶原交联N端肽进行测定,计算骨桥蛋白/基质金属蛋白酶3比值。 结果与结论：骨质疏松组中血清骨桥蛋白和基质金属蛋白酶3的水平高于正常组(P < 0.05)。绝经后妇女血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关 (P < 0.05),与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐比值呈明显正相关性(P < 0.05)。骨质疏松组中血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关 (P < 0.05),与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐水平比值存在明显正相关性(P < 0.05)。提示绝经后妇女血清骨桥蛋白水平和骨桥蛋白/基质金属蛋白酶3比值升高与绝经后骨质疏松症伴随骨代谢转换过程增快有关。     

重组人骨形态发生蛋白2及制动因素对兔肌腱端重建的影响*

背景：骨-肌腱结合结构的重建可能类似于软骨内成骨,只有形成坚固的止点,重建的韧带才能够真正发挥其生理功能。重组人骨形态发生蛋白2(recombinant human bone morphogenetic protein-2,rhBMP-2)可使未分化间质细胞、成纤维细胞、成肌细胞及骨髓的基质细胞逆转分化为骨系细胞。 目的：观察rhBMP-2和制动因素对肌腱止点结构重建的影响。 方法：新西兰白兔建立肌腱止点结构重建模型后,随机分成3组。向rhBMP-2短期制动组和rhBMP-2长期制动组实验兔靠近胫骨隧道入口的屈趾总腱内注入重组人骨形态发生蛋白2溶液20 µL,模型组不予注射。术后rhBMP-2短期制动组术肢石膏固定1周后拆除;rhBMP-2长期制动组和模型组兔术肢全程石膏固定。各组分别于手术后2,4,8周通过免疫组化法和RT-PCR测定隧道入口部肌腱中的Ⅰ,Ⅱ型胶原、骨碱性磷酸酶和骨钙素的表达。 结果与结论：rhBMP-2可使肌腱止点结构重建兔Ⅰ型胶原、骨碱性磷酸酶和骨钙素表达水平随时间的延长而增加,而Ⅱ型胶原在术后增加至4周时表达至峰值,8周表达有所下降。注射rhBMP-2未对腱重建兔Ⅰ型胶原mRNA表达产生明显变化;而注射rhBMP-2可使Ⅱ型胶原、骨碱性磷酸酶和骨钙素mRNA表达显著增加(P < 0.05),减少制动时间也能使Ⅱ型胶原、骨碱性磷酸酶和骨钙素mRNA表达显著增加(P < 0.05)。rhBMP-2能促进Ⅰ,Ⅱ型胶原、骨碱性磷酸酶和骨钙素的表达,并具有诱导肌腱内异位软骨成骨的作用,使肌腱端结构重建成为可能;长时间制动阻碍肌腱附着点的重建。 关键词：肌腱止点;重组人骨形态发生蛋白2;胶原;碱性磷酸酶;骨钙素;肌肉肌腱;组织工程     

恒定磁场中大鼠成骨细胞的增殖和功能活性

背景：磁场对成骨细胞生物学的影响存在一定的分歧。 目的：探讨不同强度恒定磁场作用不同时间后成骨细胞增殖和功能活性的改变。 方法：用体外培养的SD大鼠成骨细胞第3~5代分别在0,5,22,86,135 mT恒定磁场下培养,观察8,12,24 h后细胞增殖和凋亡变化及细胞上清液中骨钙素及Ⅰ型前胶原C端前肽的表达。 结果与结论：磁场作用8,12 h后,5,22,86,135 mT磁场培养的细胞增殖指数均高于对照组(P < 0.05),作用24 h时,仅5 mT组高于对照组(P < 0.05)。而0,5,22,86,135 mT恒定磁场下培养8,12,24 h的凋亡百分数差异无显著性意义。磁场作用8 h后,22,86,135 mT组骨钙素分泌量均高于对照组(P < 0.05);作用24 h后,135 mT组骨钙素分泌量则明显低于对照组(P < 0.05);而磁场作用8,12 h后,22,86 mT组Ⅰ型前胶原C端前肽分泌量明显高于对照组(P < 0.05),作用24 h后,135 mT组Ⅰ型前胶原C端前肽分泌量则明显低于对照组(P < 0.05)。表明低强度磁场、短时间作用可促进成骨细胞的增殖及成骨物质的分泌,而高强度磁场或磁场暴露时间过长则抑制成骨细胞增殖及成骨物质的分泌。     

基质金属蛋白酶和胶原在创伤关节软骨组织中的表达*☆

背景：研究发现,基质金属蛋白酶和胶原参与关节软骨组织机体生理重建及病理破坏。 目的：观察膝关节骨软骨缺损及表面软骨缺损动物模型关节软骨组织中胶原及基质金属蛋白酶的表达变化。 方法：雌性SD大鼠48只随机分为3组：骨软骨缺损组在双膝关节制作骨软骨缺损模型,表面缺损组在双膝关节制作表面软骨缺损,对照组双膝关节制作关节囊切开。分别于术后4、8、12周取股骨髁标本,行苏木精-伊红染色,免疫组化检测Ⅰ型胶原、Ⅱ型胶原、基质金属蛋白酶3的表达。 结果与结论：骨软骨缺损组术后4周缺损中有少量新生组织生成,8及12周可见到纤维组织填充,修复组织细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,关节软骨组织中基质金属蛋白酶3表达增高。表面缺损组表面软骨缺损4及8周未见修复迹象,12周可见微量纤维组织填充,细胞外基质Ⅰ型胶原免疫组化染色阳性,Ⅱ型胶原免疫组化染色阴性,术后表面缺损组关节软骨组织基质金属蛋白酶3表达增高。对照组关节软骨组织Ⅰ型胶原免疫组化染色阴性,Ⅱ型胶原免疫组化染色阳性,基质金属蛋白酶3低表达,无形态学异常改变。说明机械性损伤可以导致关节软骨细胞外基质成分发生改变,丧失其原有的生物学特性而退变,基质金属蛋白酶3在损伤后的软骨组织中表达增高,使细胞外基质的降解增加,是导致关节软骨退变的重要因素。     

转化生长因子β1与骨生化指标和骨密度的关系

背景： 转化生长因子β1是一种重要的调节骨构塑的细胞因子,其是否能作为反应骨转换的敏感因子尚不清楚。 目的：探讨转化生长因子β1与骨形成、骨吸收指标,以及腰椎正位骨密度间的关系。 方法：实验共纳入来自长沙的健康妇女663名,年龄20~80岁。采用ELISA法测定空腹血清转化生长因子β1、骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽的水平,同时应用双能X射线骨密度仪测定腰椎正位的骨密度。并分析转化生长因子β1与其他各指标的相关性。 结果与结论：检测结果显示30~39岁,40~49岁年龄段妇女的血清转化生长因子β1水平最高,转化生长因子β1水平与年龄呈负相关,与体质量指数无相关。校正体质量指数后发现,转化生长因子β1与骨特异性碱性磷酸酶和Ⅰ型胶原羧基末端肽负相关,校正体质量指数和年龄后血清转化生长因子β1水平与腰椎正位骨密度正相关。说明转化生长因子β1能动态地反映骨转换情况。     

低血磷性骨软化症1例

报道1例低血磷性骨软化症，男，36岁，因全身骨痛5年入院。曾查“抗O”，血沉及类风湿因子、肝肾功能、血沉、尿本周蛋白及甲状旁腺激素等均正常，多次查血磷低、血钙正常，碱性磷酸酶升高。为进一步明确患者血清骨生化标志物及病理微结构，用ELISA法检测血清I型胶原N–末端交联顶端肽、骨源性碱性磷酸酶、骨钙素均升高。X射线示双股骨颈病理性骨折、骨密度普遍减低，骨小梁和骨皮质边缘模糊。髂骨活检，石蜡包埋，Golder三色法染色，可见患者的类骨质层明显堆积。显微CT扫描骨微结构，骨小梁厚度、数目明显减少，骨小梁间隔明显增大。     

仙灵骨葆治疗骨质疏松大鼠：血清学及骨组织形态计量学评价

背景：目前对于骨质疏松的治疗多为抑制骨吸收,有研究报道仙灵骨葆可促进骨形成,但具体机制不清。 目的：通过干预去卵巢大鼠骨质疏松动物模型,探讨仙灵骨葆对骨质疏松大鼠骨量、生物力学性能及骨代谢的影响。 方法：将24只大鼠随机分为正常对照组、模型组和仙灵骨葆组。除正常对照组外,其他2组行卵巢切除。6周后仙灵骨葆组给予仙灵骨葆干预,模型组给予等量双蒸水。4周后各组留取尿液、血清检测血Ⅰ型原胶原氨基端延长肽、尿脱氧吡啶诺啉排泄率和Ⅰ型胶原氨基末端肽排泄率。取各组左侧股骨行骨密度测定,取左侧胫骨制备硬组织不脱钙切片,行骨组织形态计量学检测。 结果与结论：与模型组比较,仙灵骨葆组血Ⅰ型原胶原氨基端延长肽、尿脱氧吡啶诺啉排泄率、尿Ⅰ型胶原氨基末端肽排泄率,破骨细胞数、骨吸收周长百分数显著降低(P < 0.05),而远端骨密度和骨小梁体积均显著增高(P < 0.05),结果证实,仙灵骨葆可抑制骨吸收,促进骨形成,降低去卵巢大鼠骨转换水平,进而部分阻止其骨量丢失。     

脑卒中病人肢体瘫痪后骨密度与骨代谢的变化

目的 探讨脑卒中病人肢体瘫痪后骨密度与骨代谢的变化。方法 2011年6月至2014年6月收治首次发病脑卒中268例,发病7 d内、6个月、12个月检测血钙、血磷;采用酶联免疫吸附测定法检测血清骨钙素（BGP）、Ⅰ型前胶原氨基端前肽（PINP）、Ⅰ型胶原交联末端肽（CTX）、25-羟基维生素D3[25（OH）D3]水平;采用氯胺T氧化法测定尿脱氧吡啶磷（Dpd）;用苦味酸法测定肌酐（Cr）水平;采用双能X线骨吸收测量仪测定健侧与患侧髋部骨密度与腰椎骨密度。结果 发病6、12个月血钙、血清CTX均比发病7 d明显升高（P<0.05）;发病12个月尿Dpd/Cr比发病7 d明显升高（P<0.05）;发病12个月血磷比发病7 d明显降低（P<0.05）;发病6、12月血清BGP、PINP比发病7 d明显降低（P<0.05）;发病12个月血25（OH）D3比发病7 d明显降低（P<0.05）。发病6、12个月患侧股骨颈骨密度、腰椎骨密度比发病7 d降低明显（P<0.05）。结论 脑卒中肢体瘫痪后体内骨吸收活性显著增强,骨形成活性降低,股骨颈与腰椎骨密度降低,瘫痪侧股骨颈骨密度降低幅度更大。     

功能性矫治器引导下颌前伸后咀嚼肌中基质金属蛋白酶抑制因子及Ⅳ型胶原参与咀嚼肌的适应性变化*☆

背景：功能性矫治器引导大鼠下颌矫形治疗中，咀嚼肌也会发生适应性变化和改建，基质金属蛋白酶参与其中变化。 目的：观察功能性矫治器引导大鼠下颌前伸后咀嚼肌中基质金属蛋白酶抑制因子及其底物作用蛋白Ⅳ型胶原表达。 方法：4 周龄健康雄性SD 大鼠随机分为实验组和对照组。实验组每日白天戴矫治器10~12 h。采用免疫组织化学方法观察戴矫治器后3，7，14，21 d大鼠二腹肌前腹中基质金属蛋白酶抑制因子1，2及Ⅳ型胶原的表达。 结果与结论：实验组和对照组大鼠二腹肌前腹中基质金属蛋白酶抑制因子1，2及Ⅳ型胶原均有表达。但实验组IV型胶原、基质金属蛋白酶抑制因子1，2表达明显增强，表明功能性矫治器引导大鼠下颌前伸后咀嚼肌中 基质金属蛋白酶抑制因子1，2及Ⅳ型胶原参与了咀嚼肌的适应性变化。 关键词：咀嚼肌；基质金属蛋白酶抑制因子1；基质金属蛋白酶抑制因子2；Ⅳ型胶原；下颌前伸     

骨髓脂肪细胞向成骨细胞的转分化

背景：骨髓脂肪细胞、成骨细胞共同来源于骨髓基质细胞,二者存在基因同源性,在一定的条件下可以相互转分化。 目的：观察骨髓细胞源性脂肪细胞在成骨诱导分化培养条件下转分化为成骨细胞的活性,探索股骨头坏死细胞水平治疗的新途径。 方法：将前脂肪细胞3T3-L1分别进行成骨诱导培养和成脂诱导培养。培养后不同时间点观察细胞形态的变化;并于诱导培养后5,21 d分别进行实时定量-聚合酶链反应检测成骨、成脂分化过程中,细胞中Runt相关基因转录因子2、氧化物增殖体激活物受体γ2、骨钙素和Ⅰ型胶原mRNA表达。并于成骨、成脂培养21 d后采用Wertern-blot法检测相关蛋白的表达。培养细胞爬片,分别进行碱性磷酸酶、钙结节茜素红、油红O染色,观察3T3-L1成骨转分化情况以及成骨细胞活性表达。 结果与结论：3T3-L1在成骨诱导培养5 d后,细胞由圆形逐渐演变成纺锤形和梭形;实时定量-聚合酶链反应检测结果与对照组相比,氧化物增殖体激活物受体γ2 mRNA表达减弱,而Runt相关基因转录因子2、骨钙素和Ⅰ型胶原mRNA表达微量增强。至21 d时,这种表达改变更加明显;Western-blot显示,Runt相关基因转录因子2、骨钙素和Ⅰ型胶原蛋白量增加,而氧化物增殖体激活物受体γ2微量甚至无表达;碱性磷酸酶染色阳性表达较多,茜素红钙结节染色可见多个散在分布的钙结节;油红O染色微量脂滴。提示小鼠骨髓基质细胞源性前脂肪细胞3T3-L1在成骨诱导培养下,可在一定程度上转分化为有生物活性的成骨细胞;小鼠骨髓基质细胞的脂肪细胞和成骨细胞二者之间存在着可塑性。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.