肠道菌群与非酒精性脂肪肝病相关性研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)发病机制尚未完全阐明,目前广为接受的是“二次打击”学说,近年来关于肠道菌群与NAFLD的研究不断深入,充实和发展了“二次打击”学说,也为NAFLD的治疗提供了新思路。本文就肠道菌群与NAFLD相关性的研究进展及益生元、益生菌治疗NAFLD进展进行综述。     

抗骨质疏松药物应用的依据：骨生化代谢标志物及骨组织病理学

背景：目前国际上公认双能X射线吸收测定法为诊断骨质疏松症的金标准,但常由于测量部位异位骨化、骨质增生等因素使得测量结果存在误差。目的：探讨骨代谢标志物在老年骨质疏松骨折诊疗中的临床意义以及它与骨密度和骨组织形态病理学改变的相关性。方法：选取50例需行手术治疗的老年骨质疏松骨折患者,行骨生化4项检测,其中抗酒石酸酸性磷酸酶5b(TRACP 5b)检测值明显增高患者25例(标记为抗酒石酸酸性磷酸酶5b升高组),骨碱性磷酸酶(BAP)检测值明显升高患者25例(标记为骨碱性磷酸酶升高组)。术中抽取两组各8例患者骨折断端部分骨组织,苏木精-伊红染色普通光镜检查和扫描电镜检查病理学改变。术后,抗酒石酸酸性磷酸酶5b升高组患者使用鲑鱼降钙素抗骨质疏松治疗,骨碱性磷酸酶升高组患者使用骨肽注射液抗骨质疏松治疗,6个月后再次检测骨密度和骨生化4项。结果与结论：两组患者术前骨密度和骨生化4项检查结果相比较差异无显著性意义(P > 0.05)。抗酒石酸酸性磷酸酶5b升高组患者骨折断端骨组织病理检查示成骨细胞减少、破骨细胞增多;骨碱性磷酸酶升高组患者骨折断端骨组织病理检查示成骨细胞减少;两组骨小梁/骨面积比值均降低,且抗酒石酸酸性磷酸酶5b升高组较骨碱性磷酸酶升高组降低程度差异有显著性意义(P < 0.05)。扫描电镜检查示两组破骨细胞都较正常组活跃,抗酒石酸酸性磷酸酶5b升高组骨小梁较骨碱性磷酸酶升高组稀松明显,吸收空泡增大。两组于术后使用抗骨质疏松药物治疗,两组治疗前与治疗后骨密度和骨生化4项检测结果差异有显著性意义(P < 0.05)。结果显示：①骨代谢标志物检测能明确患者骨组织是以成骨细胞功能和数量减低还是以破骨细胞功能和数量增加为主,以便指导临床针对性使用抗骨质疏松药物。②骨折断端骨组织形态病理学检查能更好地反映患者骨组织内成骨细胞、破骨细胞和骨小梁等状况。骨质疏松患者针对性使用抗骨质疏松药物治疗能提高疗效、降低相关并发症。     

Wnt信号通路拮抗剂Dkk1调节骨代谢的最新进展

背景：Dickkopf-1(Dkk1)是一种Wnt信号通路的可溶性胞外抑制剂,可以通过竞争性地结合Wnt蛋白的共同受体低密度脂蛋白受体相关蛋白5/6来阻断经典Wnt/β-catenin途径,进而调控Wnt/β-catenin途径下游靶基因的转录。 目的：将Dkk1调节骨代谢的最新进展作一综述,为骨疾病的抗Dkk1治疗提供理论基础。 方法：电子检索CBM和Medline数据库中1995至2012年关于Dkk1对骨代谢调节作用的文章,检索词为“Dkk1;骨重塑;骨疾病”和“Dkk1; bone remodeling; bone diseases”。 纳入关于Dkk1调节骨代谢的高质量文献,排除重复发表文献。 结果与结论：初始检索118篇文献,按纳入排除标准筛选后,选出36篇文献进行综述。骨组织时刻处于动态的重塑过程中,成骨细胞和破骨细胞的相互作用决定着骨形成和骨吸收之间的平衡。Dkk1可阻断Wnt/β-catenin信号通路、抑制骨形成,同时又通过与骨保护素/核因子ΚB受体活化因子配体/前体细胞表面受体轴的串话作用促进破骨细胞的分化与成熟。促进骨形成、抑制骨吸收是抗Dkk1治疗骨代谢相关疾病引起骨质缺失的主要机制与思路,且临床试验结果良好,Dkk1是一个非常有潜力的骨代谢疾病治疗靶点。     

成骨细胞、破骨细胞与酒精性股骨头坏死的关联性： 预防与靶向治疗的新思路

BACKGROUND: Alcohol-induced femoral head necrosis is a bone metabolism disease that involves a series of alcoholism-induced pathological changes, including degeneration, necrosis and deposition of adipocytes and osteoporosis, and trabecular collapse in the subchondral bone trabeculae of the femoral head. OBJECTIVE: To introduce the correlation of osteoblasts and osteoclasts with alcohol-induced femoral head necrosis. METHODS: The first author searched relative articles in PubMed and CNKI databases published before May 2016 using the keywords of “osteoblast, osteoclast, alcohol-induced ONFH, bone metabolism” in English and Chinese, respectively. 133 literatures were retrieved and 38 literatures were in accordance with the inclusion criteria. RESULTS AND CONCLUSION: During the process of bone metabolism, osteoblasts and osteoclasts exhibit interaction in term of cell number and viability. In-depth study on osteoblasts, osteoclasts and their interaction cannot only give insight into the pathogenesis and repair of alcohol-induced femoral head necrosis, but also provide new ideas and strategies for prevention and target treatment of bone metabolic diseases. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

OPG-RANKL-RANK信号系统是调节破骨细胞及骨质疏松症的重要途径

背景：OPG-RANKL-RANK信号系统在破骨细胞对于骨吸收机制中的重要作用。 目的：归纳总结OPG-RANKL-RANK信号系统在破骨细胞、骨质疏松症中的表达,以及OPG-RANKL-RANK信号系统靶向治疗的前瞻性。 方法：在国内外期刊数据库中检索近10年内国内外文献,按关键词：骨保护素,RANKL,RANK,破骨细胞,骨质疏松症;OPG,osteoclast,osteoporosis,检索相关文献,筛选出符合纳入标准的文献,对文献进行质量评估后采纳。 结果与结论：OPG-RANKL-RANK信号系统以及相关联的信号途径是介导破骨细胞发育、成熟的重要信号途径,并且是导致骨质疏松症的机制,在基因及分子水平上,靶向治疗骨质疏松症已成为人们的关注点。基于OPG-RANKL-RANK信号系统靶向可成为治疗为骨质疏松症的研究提供平台,OPG-RANKL-RANK信号系统是调控破骨细胞及骨质疏松症的重要途径。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

补肾接骨中药对骨折修复的成骨作用及机制

背景：骨折愈合是成骨细胞与破骨细胞耦联相互作用相互影响促进骨质生长的过程,其中成骨细胞介导骨的形成,破骨细胞介导骨吸收,使骨重建处于一种动态平衡中,于动态平衡环境中促进骨生长,而目前研究多数倾向于单独的成骨或者破骨机制,但会忽略这两种细胞共同存在的环境下相互作用机制。 目的：观察补肾接骨中药对成骨与破骨细胞耦联中骨护骨素-核因子κB受体激活剂的配基-核因κB受体活化因子的影响及其在骨折治疗中的作用机制。 方法：分离小鼠成骨、破骨细胞并体外细胞培养,建立小鼠“成骨-破骨细胞共育系”作为研究平台,补肾接骨中药1.25,2.5,6.25 g/(kg•d)灌胃,空白对照组给予同等体积的生理盐水灌胃,每日1次,连续7 d。 结果与结论：共育培养24 h后,成骨细胞内碱性磷酸酶水平明显高于单纯培养的成骨细胞(P < 0.05)。实时PCR检测显示,共育体系细胞中碱性磷酸酶、Runx2及骨护骨素表达增加(P < 0.05),呈剂量依赖性(P < 0.05)。Western-blot检测显示,高浓度[6.25 g/(kg•d)]中药能明显促进骨护骨素、核因子κB受体激活剂的配基的表达,抑制核因子κB受体活化因子蛋白表达(P < 0.05)。结果证实,补肾接骨中药可动态调节骨护骨素-核因子κB受体激活剂的配基-核因子κB受体活化因子信号通路,对促进骨组织重建与恢复有着积极的作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

骨折合并脑损伤对骨愈合和骨代谢的影响

背景：骨折周围神经损伤能够有效抑制破骨细胞活动,促进骨折早期愈合。目的：观察了大鼠肢体骨折合并脑损伤对骨密度、骨微结构、骨生物力学特征和骨代谢影响。 方法：63只大鼠随机分为假手术组、单纯骨折组和脑损伤合并骨折组。在术后3周、6周和3个月分批麻醉处死动物保存骨骼和血清标本,检测骨密度、骨微结构和生物力学性能以及血清Ⅰ型胶原氨基末端肽和骨钙素水平的变化。 结果与结论：与单纯骨折组相比,在造模3周和6周后,脑损伤合并骨折组胫骨近端的骨密度、松质骨微结构骨体积分数、骨小梁厚度、胫骨皮质骨截面总面积和骨髓腔面积、胫骨极限载荷和极限应力、血清原氨基末端肽和骨钙素水平均显著增高(P < 0.05),造模后3个月,3组间上述指标均差异无显著性意义。结果证实,脑损伤可增加骨折局部骨密度,改善骨微结构,提高生物力学性能,以此促进骨折局部的骨愈合和骨代谢。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

肠道菌群及其代谢产物靶向治疗心力衰竭的研究进展

心力衰竭是心血管疾病的终末期,是现今全球发病率和病死率的主要原因.越来越多的研究表明:肠道菌群失调及肠道菌群代谢产物与心力衰竭的发生发展之间存在着显著相关性,因此针对肠道菌群及其代谢产物的靶向治疗有望成为改善心力衰竭的新的治疗策略.现就肠道菌群及其代谢产物在心力衰竭中的作用以及靶向治疗心力衰竭的研究进展作一综述.     

益生元对婴儿生长及肠道菌群的影响

目的:探讨益生元GOS/lcFOS对婴儿生长及肠道菌群的影响。方法:健康足月儿140例,分别接受含有与不含有GOS/lcFOS的标准配方奶,观察他们在实验结束时的生长情况及大便特征,以及试验第四周时大便菌群的情况。结果:婴儿对GOS/lcFOS有良好的耐受性,试验组与对照组婴儿的生长情况相近,试验组大便次数多于对照组(P=0.031),并且前者的大便比后者的软。试验组大便梭菌属明显少于对照组(P=0.042)。试验组的大便双歧杆菌要多于对照组,不过差异无统计学意义(P=0.262)。试验组的大肠杆菌少于对照组,差异无统计学意义(P=0.312)。结论:婴儿对益生元GOS/lcFOS有良好的耐受性。GOS/lcFOS不影响婴儿的正常生长,并可抑制肠道梭菌属的生长。     

骨水泥、钉道植骨强化动力髋螺钉固定修复老年骨质疏松性股骨转子间骨折

背景：对于老年骨质疏松性髋部骨折的动力髋螺钉固定,如能避免使用过程中造成的骨量丢失,或是采用其他手段增加固定螺钉把持力,将改善动力髋螺钉固定的治疗效果。 目的：对比研究3种固定方式修复老年骨质疏松性股骨转子间骨折的效果。   方法：回顾性分析近5年来采用常规动力髋螺钉内固定、骨水泥强化后动力髋螺钉固定及主钉道压配植骨配合动力髋螺钉固定3种固定方式治疗老年骨质疏松性股骨转子间骨折患者的资料,分别设为对照组、骨水泥组和植骨组。 结果与结论：经固定后2年随访,植骨组、骨水泥组和对照组Harris髋关节功能评分优良率分别为95%,80%,70%。植骨组骨折临床愈合时间明显缩短(P < 0.05),出现螺钉固定失败情况与骨水泥组相当。对照组较其他2组相对更多出现退钉等内固定失败情况。结果表明,与其他常规动力髋螺钉内固定、骨水泥强化后动力髋螺钉固定方式相比较,主钉道压配植骨配合动力髋螺钉内固定的疗效及安全性更好。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

培哚普利对维甲酸所致骨质疏松模型大鼠骨代谢的影响

BACKGROUND: Renin-angiotensin-aldosterone system existed in bone tissue. Recent studies on antihypertensive drugs found that angiotensin converting enzyme inhibitor type antihypertensive drug was possibly effective for osteoporosis. Perindopril is one of the commonly used antihypertensive drugs. Whether perindopril affected bone metabolism or could be used in anti-osteoporosis has not been reported.     

2型糖尿病大鼠骨质疏松模型的建立

BACKGROUND: Diabetes mellitus can give rise to bone metabolic disorders that may involve long-term hyperglycemia, hypoglycemic agents, diet control, estrogen, insulin-like growth factor, leptin, body mass, sex and age.     

骨微结构与微损伤检测方法的研究与进展

BACKGROUND: Bone fragility and poor bone quality due to osteoporosis are a major and increasing concern. Bone microarchitecture and microdamage, the important factors of bone quality, their detection technology and instrument have experienced a long development process.     

甲状旁腺激素1-34、阿仑膦酸钠、辛伐他汀治疗大鼠骨质疏松效果的比较

BACKGROUND:Bone resorption drugs in the treatment of osteoporotic fracture are still controversial. The development of new drugs, especially drugs in the promotion of bone formation, become more important and urgent.  OBJECTIVE: To compare the effects of parathyroid hormone (1-34), alendronate sodium and simvastatin on bone loss in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats aged 3 months were randomized into five groups of six animals in each group. All rats but those in sham group received dual ovariectomy (OVX) and treated by vehicle (OVX+V), parathyroid hormone (1-34) (5 days per week at a dose of 20 μg/kg, OVX+P), alendronate sodium (70 μg/kg/wk, OVX+A), simvastatin (5 mg/kg/d, OVX+S). Three months later, all rats were sacrificed. Dual energy X-ray method was used to measure bone density of L4 vertebra. Bone histomorphometry was utilized to analyze cancellous bone mass and bone microstructure. Compression test was performed on the L5 vertebra for the maximum loading and elastic modulus.   RESULTS AND CONCLUSION:(1) Bone density: The bone density from high to low levels was OVX+P group, sham group, OVX+A group, OVX+S group, and OVX+V group. No significant difference in bone density was detectable between the OVX+P and sham groups, but significant differences in bone density were determined between any other two groups (P < 0.05). (2) Bone histomorphometry: Relative volume of trabecular bone was significantly lower in the OVX+V group than in other groups. Relative volume of trabecular bone was remarkably higher in the OVX+P group than in the OVX+A group and OVX+S group. (3) Biomechanical properties: Biomechanical properties were noticeably lower in the OVX+V group than in other groups. Biomechanical properties were remarkably higher in the sham group and OVX+P group than in the OVX+S group and OVX+A group. (4) These findings indicated that under the dosage and intervention period used in the present study, parathyroid hormone (1-34), alendronate sodium and simvastatin showed anti-osteoporosis effect on OVX rats in a descending manner. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Bone metabolism before and after irradiation with ultraviolet light

Summary The beneficial effects of ultraviolet light on cutaneous vitamin D synthesis, calcium metabolism, and bone formation are well known. Regarding the increasing fear of side effects from ultraviolet B (UV-B), lamps with less energy in the UV-B range have been developed. Two spectra with differences in the emission of UV-B have therefore been evaluated for their influence on calcium metabolism. A group of 24 healthy male volunteers was subdivided into two treatment groups. Group 1 was exposed to lamps with higher energy of total UV-B but less energy at the wavelengths below 300 nm than the lamps used in group 2. All subjects were irradiated ten times within 12 days. Exposure time was 3 min in the first session and time of exposure was increased by 10% in every following irradiation (suberythematous doses only). Before the first irradiation, 3 days after the last exposure, and after 4 more weeks, the serum parameters of bone metabolism were determined by standard laboratory methods. Significantly increased levels of 25-hydroxyvitamin D₃ were found in both groups. There was only a slight increase of 1,25-dihydroxyvitamin D₃. Parathyroid hormone decreased significantly in group 2 only. The data would suggest beneficial effects on bone metabolism for both regimens. The observed effects were more pronounced when shorter wavelengths (group 2) were applied, although the total energy of UV-B was lower in these lamps.     

牙槽骨骨密度与甲状腺激素的影响

BACKGROUND: Overproduction of thyroid hormones is shown to increase the activities of osteoblasts and osteoclasts, stimulating bone resorption and transformation. Inadequate compensation of increased bone resorption by bone transformation results in an increased loss of bone mass. OBJECTIVE:To investigate the effects of hyperthyroidism on the density of the alveolar bone. METHODS:Twenty-four New Zealand rabbits were equally randomized into hyperthyroidism group and control group. Rabbits in the hyperthyroidism group or control group were daily injected intraperitoneally with 50 μg/kg levothyrocine diluted in physiological saline solution or equal volume of physiological saline. At 8 weeks after treatment, serum levels of thyroid hormones (FT3 and FT4), alkaline phosphatase, magnesium and calcium, phosphorus were determined; meanwhile, the bone densities of the lumbar vertebra, mandible, bilateral distal femur were determined by dual energy X-ray absorptiometry and the correlation analysis was performed. RESULTS AND CONCLUSION: At 8 weeks after treatment, serum levels of FT3, FT4, alkaline phosphatase calcium, phosphorus, and magnesium in the hyperthyroidism group were significantly increased (P < 0.01), while the bone densities of the lumbar vertebra, mandible, bilateral distal femur were significantly decreased (P < 0.05), compared with the control group. Bone density of the mandible was positively correlated with the bone density the lumbar vertebra and bilateral distal femur. These findings suggest that the changes in FT3 and FT4 are sufficient for the diagnosis of hyperthyroidism. Hyperthyroidism results in the decreased density of the alveolar bone, indicating the occurrence of osteoporosis. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Bone tissue engineering in osteoporosis

Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age.     

阿仑膦酸钠与激素替代疗法治疗骨质疏松症的比较

文章快速阅读： 文题释义： 激素替代疗法(hormone replacement therapy,HRT)：是指通过补充激素来治疗激素分泌减退或者缺乏所引起的疾病的治疗方法。广义上的HRT涵盖所有的激素。狭义上的HRT多是针对女性激素,特别是指雌激素替代疗法(estrogen replacement therapy,ERT)。美国公布的研究结果显示,虽然激素替代疗法能帮助中老年妇女改善更年期不适症状,但这种疗法也会增加女性患痴呆症的风险。新结果再次表明需要对激素替代疗法的利弊进行重新评估。 骨质疏松症：是由于多种原因导致的骨密度和骨质量下降,骨微结构破坏,造成骨脆性增加,从而容易发生骨折的全身性骨病。绝经后骨质疏松症一般发生在妇女绝经后5-10年内。摘要 背景：研究表明雌激素、双膦酸盐、降钙素等可在一定程度上提高骨密度和降低骨折发生率,其中阿仑膦酸钠作为临床最常用的双膦酸盐类药物得到人们的关注。 目的：对比分析阿仑膦酸钠与激素替代疗法治疗绝经后骨质疏松症的疗效。 方法：绝经后骨质疏松症患者198例随机平均分为2组,每组99例,阿仑膦酸钠组口服阿仑膦酸钠,每周70 mg,连续1年;激素代替疗法组口服替勃龙片2.5 mg/d,连续1年,比较治疗前后2组的骨密度、性激素水平,并比较2组患者的不良发应发病率及对骨代谢标志物的影响,同时进行疼痛改善评价。 结果与结论：①治疗之后2组的股骨颈及L1-4的骨密度均较治疗前有所改善(P < 0.05);②激素代替疗法组治疗后血清雌激素和孕酮浓度均有下降的趋势,皮质醇有升高的趋势(P < 0.05);③目测类比评分阿仑膦酸钠组优于激素代替疗法组(P < 0.05);④阿仑膦酸盐组血清Ⅰ型原骨胶原 N端肽、血清β胶原降解产物治疗后较激素代替疗法组下降明显(P < 0.05)、阿仑膦酸钠组血清骨源性碱性磷酸酶和血清骨钙素较激素代替疗法组上升(P < 0.05);⑤激素替代疗法组的恶心、乏力等不良发应发病率高于阿仑膦酸钠组(P < 0.05);⑥结果说明,阿仑膦酸钠与激素替代疗法治疗绝经后骨质疏松症均可有效的提高骨密度,促进骨形成,阿仑膦酸钠对患者激素水平影响较小且不良反应小,其治疗效果更佳。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程 ORCID: 0000-0003-1435-913X(苏凡)     

骨组织工程基质材料的现状及展望

通过阐述理想骨组织工程细胞外基质材料的要求,并总结生物类材料、生物陶瓷类材料、聚合物类材料和复合类材料在骨组织工程中用作细胞外基质材料的优缺点,认为理想的骨组织工程细胞外基质材料最好由生物陶瓷类材料、人工合成聚合物类材料或天然聚合物类材料组成,并含有最佳的生长因子缓释系统的多孔三维立体泡沫,这种复合型细胞外基质材料的研制是骨组织工程研究中十分重要而迫切的任务。