维生素D3在移植免疫中的应用进展

维生素D₃是维持人体正常生理功能的重要维生素,其代谢物及类似物具有强大的抗炎活性。维生素D₃可在人体内活化转化为类固醇激素1α,25-二羟维生素D₃,而1α,25-二羟维生素D₃可以激活转录因子维生素D受体,参与细胞代谢的调控,发挥免疫调节作用,这对维持机体生理健康至关重要。目前,越来越多的研究认为1α,25-二羟维生素D₃在器官移植免疫调节及耐受中具有重要作用。因此,本文就1α,25-二羟维生素D₃的概述及生理作用、维生素D₃的免疫调节作用及维生素D₃在临床器官移植中的应用进行综述,总结维生素D₃在诱导移植免疫耐受中的应用价值,以期为促进维生素D₃在移植免疫中的应用提供参考。     

羟基磷灰石掺锶对成骨细胞增殖分化及矿化影响的实验研究

[目的]探讨羟基磷灰石(HA)中掺锶对成骨细胞增殖、分化和矿化的影响,以及HA材料中适宜的掺锶量。[方法]用掺锶量分别为1%,5%和10%的HA生物陶瓷粉末及纯HA生物陶瓷粉末制备的浸提液培养SD大鼠成骨细胞,在不同时间点检测成骨细胞增殖、碱性磷酸酶(ALP)活性、核心结合因子(cbfal)基因表达,以及矿化结节形成的情况。[结果]各组成骨细胞的增殖无明显差别(P0.05);细胞培养第14、21d,掺锶各组成骨细胞的ALP活性、cbfalmRNA表达,及矿化结节数量等方面均显著高于HA组(P0.01),其中以掺锶量5%组最高,但与10%组相比无显著差异。[结论]HA中掺锶能上调成骨细胞cbfalmRNA的表达,促进成骨细胞分泌碱性磷酸酶,从而促进成骨细胞的分化、矿化,促进骨形成。详细的作用机制及HA中最佳的掺锶量尚需进一步的研究。     

阿胶强骨口服液对去卵巢骨质疏松大鼠骨密度、生物力学、25-(OH)D3和1,25-(OH)2D3的影响

目的：研究阿胶强骨口服液对去卵巢骨质疏松大鼠骨密度（BMD）、生物力学、25-（OH）D3和1，25-（OH）2D3，的影响，探讨阿胶强骨口服液治疗原发性骨质疏松症的疗效机制。方法：4月龄健康雌性SD大鼠36只，随机分为3组，每组12只，分别为模型组，假手术组，阿胶强骨口服液治疗组。除假手术组外所有大鼠手术摘除双侧卵巢后导致雌激素缺失从而诱导骨质疏松症模型，分别在实验的第4、8、12周采用DEXA法分析股骨头及粗隆部的骨密度，生物力学技术分析股骨头生物力学参数，酶联免疫吸附方法检测25-（OH）D3和1,25-（OH）2D3的含量。结果：阿胶强骨口服液治疗组与模型组比较，股骨头及粗隆部骨密度明显提高（P〈0．05）；最大载荷（ML）及最大压应变（MS）等指标明显增强（P〈0．05）；血液、肝脏和肾脏组织中25-（OH）D3和1，25-（OH）2D3的含量明显提高，且组间比较差异有统计学意义（P〈0．05）。阿胶强骨口服液治疗组与假手术组比较差异无统计学意义（P〉0．05）。结论：阿胶强骨口服液在雌激素缺失早期即可在蛋白水平上调节25-（OH）D3和1，25-（OH）2D3的表达，激活骨代谢，提高骨密度，增强骨质量，起到预防骨质疏松的作用。     

慢性肾脏病患者维生素D3水平变化及其相关因素分析

目的:分析慢性肾脏病(CKD)患者活性维生素D3水平变化及其相关因素。方法:检测2013年4月~2014年6月本院新诊断的143例非透析CKD患者及19例同期健康体检者维生素D3水平,分析其与肾功能、成纤维细胞生长因子23(血FGF-23)、血钙、血磷、甲状旁腺素(PTH)等指标的关系。结果:CKD1~5期患者维生素D3水平分别为(22.03±4.39)ng/ml、(20.29±4.66)ng/ml、(16.88±3.00)ng/ml、(13.71±2.99)ng/ml、(9.76±2.97)ng/ml,与对照组(25.68±4.08)ng/ml相比,各组间维生素D3水平逐渐下降(P<0.05)。维生素D3水平与血肌酐(r=-0.676)、尿素氮(r=-0.554)、血磷(r=-0.248)、钙磷乘积(r=-0.178)、PTH(r=-0.636)、FGF-23(r=-0.690)呈负相关(P<0.05),与血钙(r=0.157)、白蛋白(r=0.164)、肾小球滤过率e GFR(r=0.759)呈正相关(P<0.05),多元逐步回归分析显示维生素D3与e GFR呈正相关,与PTH呈负相关。回归方程为Y=13.196+0.092X1-0.016X2(Y为维生素D3,X1为e GFR,X2为PTH,13.196为常数)。结论:随着CKD的进展,患者活性维生素D3缺乏日益严重,且与钙磷代谢紊乱、继发性甲旁亢及FGF-23升高相关。     

活性维生素D3抑制UUO模型大鼠肾间质纤维化作用的实验研究

目的:研究活性维生素D3[1,25(OH)2D3]在肾间质纤维化(RIF)中的保护作用,探讨1,25(OH)2D3的抗肾间质纤维化作用机制。方法:将40只SD大鼠随机分为UUO空白对照组、1,25(OH)2D3治疗组、贝那普利组、假手术组和假手术+1,25(OH)2D3组。采用单侧输尿管梗阻(UUO)致大鼠RIF模型。于术后第9周处死动物,取血标本做血钙浓度和肾功能检测。取肾组织行苏木素-伊红(HE)染色观察肾间质病理变化。免疫组化法检测HGF、TGF-β1和α-SMA蛋白表达,RT-PCR法检测肾组织HGF和TGF-β1mRNA的表达水平。结果:1,25(OH)2D3治疗组、贝那普利组血肌酐、尿素氮均较UUO空白对照组显著降低(P<0.05);各组间血钙浓度差异无统计学意义(P>0.05)。光镜下观察1,25(OH)2D3治疗组和贝那普利组RIF程度轻于UUO空白对照组。1,25(OH)2D3治疗组HGF和TGF-β1蛋白和mRNA表达水平与UUO空白对照组相比,分别显著上调(P<0.05)和下调(P<0.05)。结论:1,25(OH)2D3抑制RIF的作用与其抑制TGF-β1表达和肌成纤维细胞转分化,同时上调HGF表达有关。     

维生素D调控成骨细胞的作用机制

维生素D是体内重要调节激素．而1.25(OH)2D3是维生素D最具活性的代谢产物,它可调控骨细胞,尤其是成分细胞的功能。1.25(OH)2D3调控成分细胞是通过基因途径和非基因途径,基因途径由核内维生素D受体介夺,非基因途径与细胞膜活化有关。     

羊胎素对体外成骨细胞增殖、分化及矿化功能的影响

目的 观察羊胎素在体外对新生大鼠颅骨成骨细胞增殖、分化及矿化功能的影响。方法将提取之羊胎素稀释加入体外培养的SD新生大鼠颅骨成骨细胞体系中,终浓度分别为0.625％、1.25％、2.5％、5％和10％;加药后24、48和96 h用MTT法检测细胞的增殖并绘制生长曲线:培养5 d时用PNPP法测定细胞碱性磷酸酶(ALP)活性;培养31 d时用茜素红染色2.5％羊胎素组形成之矿化骨结节,用图像分析仪计算骨结节的面积。结果 所有含羊胎素浓度组,其MTT法测得的A值都显著高于空白对照组(P<0.01),生长曲线表现为含羊胎素组的细胞增殖加快,以2.5％浓度组最为显著;ALP结果显示,羊胎素各浓度组的碱性磷酸酶活性都显著高于空白对照组(P<0.01);茜素红染色后显示,2.5％羊胎素组所形成的骨结节面积显著高于空白对照组(P<0.01)。结论羊胎素对体外培养的SD新生大鼠颅骨成骨细胞有显著的促进增殖、分化和矿化的作用。     

一氧化氮、活性维生素D3与器官移植

一氧化氮经一氧化氮合酶产生,1,25-(OH)2D3是维生素D的生物活性形式,二者与缺 血再灌注损伤、机体免疫、移植排斥反应等关系密切,本文就此方面的研究进展作一综述。     

维生素D对骨关节炎作用的进展

骨关节炎(OA)是我国中老年人常见病、多发病之一,疾病使软骨破坏、软骨下骨质病变和关节周围骨质增生,最终导致关节疼痛、功能障碍甚至是畸形,影响患者活动能力。维生素D具有参与钙磷代谢、改善成骨细胞的活性、促进骨基质的骨化、增加骨密度以及关节软骨的转化等功能,对骨骼健康十分重要。但人体维生素D水平对OA的影响尚未明确,本文就维生素D与OA发展、关节疼痛症状、关节置换术后功能恢复以及补充维生素D后治疗效果等方面相关研究作一综述。     

NBD多肽促进成骨细胞分化的实验研究

[目的]探讨核因子κB必需分子(NF-κB essential modulator,NEMO)结合的小分子多肽(NEMO bind-ing domain,NBD)通过阻断肿瘤坏死因子-α信号通路影响成骨细胞分化的作用及其分子机制。[方法]应用BMP-2体外诱导鼠肌源细胞C2C12向成骨细胞分化模型,外源添加TNF-α和/或BMP-2细胞因子培养,通过碱性磷酸酶(ALP)活性检测,瞬时转染和基因测定,研究NBD多肽对抗NF-κB活性和改善TNF-α抑制成骨细胞分化的过程。[结果]ALP染色显示NBD多肽能明显阻断TNF-α对C2C12向成骨细胞分化的抑制而促进其分化,荧光素酶活性测定显示TNF-α降低BMP-2活性从7.12倍到1.31倍,而NBD多肽使其恢复到6.7倍和mNBD肽恢复到1.4倍。[结论]TNF-α抑制成骨细胞分化的分子生物机制是通过激活NF-kB阻碍成骨细胞的分化。NBD多肽具有对抗NF-κB活性和改善TNF-α抑制成骨细胞分化过程的作用。     

Serum vitamin D metabolites in younger and elderly postmenopausal women

Summary Previous investigations have suggested that a lower-than-normal serum 1,25(OH)₂D is found in elderly women with postmenopausal osteoporosis. We examined the fundamental aspects of this theory by investigating serum vitamin D metabolites infour representative samples of Caucasian women. These included 44 early postmenopausal women divided intotwo subgroups: fast bone losers, that is, bone loss>3%/year (n=20), and “physiological” bone loss (n=24); and 28 70-year-old women divided intotwo subgroups: with and without osteoporotic fractures. Serum 1,25(OH)₂D concentrations were virtually the same in all groups thus contradicting the previous reports of low 1,25(OH)₂D in elderly women. Furthermore, mean 25OHD and 24,25(OH)₂D did not differ between the groups. We conclude that 1,25(OH)₂D is unlikely to be significant in the development or treatment of a majority of women with postmenopausal osteoporosis.     

Clinical Controversies in Vitamin D: 25(OH)D Measurement,Target Concentration,and Supplementation

Despite a plethora of recent research and systematic reviews of available data, controversy continues to surround the definition of optimal vitamin D status, the daily intake needed, and the potential adverse health consequences of “insufficiency.” Efforts to standardize vitamin D measurement and improve understanding of the physiologic consequences of other vitamin D metabolites such as 3-epi and 24,25(OH)₂D (and potentially other vitamin D compounds) are needed. Currently, measurement of circulating 25(OH)D is accepted as the approach to define an individual's vitamin D status. However, existing 25(OH)D assays may include other vitamin D metabolites such as the 3-epimer of 25(OH)D and 24,25(OH)₂D. It seems unlikely that the controversy will soon be resolved.     

Vitamin D Metabolism and Osteomalacia in Patients with Fractures of the Proximal Femur

A high frequency of histological osteomalacia (25 per cent) was seen in patients with fractures of the proximal femur. No correlation was found between the levels of circulating 25-hydroxyvitamin D (25-OHD) or 1,25-dihydroxyvitamin D (1,25-(OH)₂D) and the bone histomorphometric changes.

The serum 25-OHD levels were normal, which excludes a dietary vitamin D deficiency or a reduced hepatic hydroxylation of the vitamin. The mean serum 1,25-(OH)₂D concentration was significantly reduced in the whole patient group, but surprisingly the levels were normal in those with histological osteomalacia, indicating that an impaired conversion of 25-OHD to 1,25-(OH)₂D was not the primary cause of the bone disease. A reduced sensitivity to 1,25-(OH)₂D might be a possible explanation for the osteomalacia.     

Retracted: CDP/cut is an osteoblastic coactivator of the vitamin D receptor (VDR)

Retraction: The following article from the Journal of Bone and Mineral Research, “CDP/Cut Is an Osteoblastic Coactivator of the Vitamin D Receptor (VDR)” by Eiji Ochiai, Hirochika Kitagawa, Ichiro Takada, Sally Fujiyama, Shun Sawatsubashi, Mi‐sun Kim,Yoshihiro Mezaki, Yu Tsushima, Ken‐ichiro Takagi, Yoshiaki Azuma, Ken‐ichi Takeyama, Kazuyoshi Yamaoka, Shigeaki Kato, Takashi Kamimura, published online on December 11, 2009 in Wiley Online Library ( wileyonlinelibrary.com ), has been retracted by agreement between the authors, the journal Editor in Chief, Thomas Clemens, the American Society for Bone and Mineral Research and Wiley Periodicals, Inc. The authors have requested the retraction based on their acknowledgement that several of the figures did not reflect the observations presented.     

Serum levels of 25-hydroxyvitamin D in postmenopausal osteoporosis

Summary Serum concentrations of 25-hydroxyvitamin D were measured in a group of women with symptomatic postmenopausal osteoporosis, assessed by bone biopsy. A competitive protein binding assay was used, which included a chromatographic step. Accurate surveys of dietary or therapeutic vitamin D intake and light environment were obtained in each patient. Women with severe postmenopausal osteoporosis were found to have significantly (P<0.001) higher serum levels of 25-hydroxyvitamin D than age-matched normal women, the mean values being 27.5 ng/ml (±13.6 SD) and 8.2 ng/ml (±5.7), respectively. The authors hypothesize that the reduction in 1,25-dihydroxyvitamin D, recently reported in postmenopausal osteoporotic women, might be responsible for the increased serum levels of 25-hydroxyvitamin D through an inadequate product inhibition of liver vitamin D 25-hydroxylase.     

老年男性骨质疏松与相关影响因素的关系

目的 测定老年男性不同年龄组骨密度及有关的影响因素,以探讨老年男性骨质疏松的发生与有关影响因素的关系,为防治老年男性骨质疏松症提供依据。方法 双能量X线骨密度测定仪测定前臂骨密度;全自动生化分析法测定血清钙（Ca)、磷（P）;放免法测定甲状旁腺素（PTH）、降钙素（CT）、1,25（OH）2D3、25（OH）D3、白介素－6（IL－6）。97例老年男性分为骨质疏松组与非骨质疏松组,并与60岁以下男性 进行比较。结果 老年男性骨密度、CT,1,25（OH2）D3、25（OH）D3随年龄增长而降低,PTH、IL－6随着年龄增长而升高（P＜0．05）。骨质疏松组与非骨质疏松组比较,PTH、IL－6二明显升高,CT、25（OH）D3、1,25（OH）2D33明显下降（P＜0．05－0．001）。结论 骨质疏松有关影响因素的改变使骨吸收增加,骨形成降低,导致骨丢失,引发骨质疏松症。     

Vitamin D deficiency in mothers of rachitic infants

Summary The existence of nutritional deficiency rickets among infants in sunny Riyadh was confirmed radiologically. Most of the rachitic infants were breast-fed, some received unsupplemented infant feeding formulae, and all live in an environment that is devoid of sunlight. Their mean age at the time of onset was 10.5 months. 25-Hydroxyvitamin D (25OHD) levels were found to be low in mothers of the rachitic infants. This maternal deficiency as a factor in pathogenesis of rickets in the infant is discussed. Proposals are made to prevent the occurrence of rickets on this scale.     

Vitamin D insufficiency in steroid-sensitive nephrotic syndrome in remission

Serum 25-hydroxyvitamin D [25(OH)D] concentrations are the best indicator of vitamin D nutritional status. We measured serum 25(OH)D concentrations in 94 healthy controls and in 41 subjects (aged 4–22 years) with steroid-sensitive nephrotic syndrome (SSNS) in remission. Children with remitted SSNS had significantly lower 25(OH)D concentrations than healthy controls (median 16.4 ng/ml versus 23.9 ng/ml, P <0.001). In a multivariable logistic regression model, the odds ratios (OR) of vitamin D insufficiency [25(OH)D <20 ng/ml] were independently increased in SSNS subjects [OR 11.2 (95% confidence interval 3.5–36.2)], non-whites [OR 12.9 (4.6–36.2)], older children [OR 1.20 per year (1.06–1.36)], and winter months [OR 6.7 (2.5–18.4)]. Within the SSNS subjects, multiple linear regression determined that serum 25(OH)D concentrations were not associated with SSNS disease characteristics measured in this study, such as duration of disease, number of relapses, cumulative glucocorticoids, and interval since last relapse. In conclusion, children with remitted SSNS have lower serum 25(OH)D concentrations than healthy controls. This difference persisted after adjusting for the potential confounding effects of age, race, season, and milk intake. Children with remitted SSNS may benefit from routine measurement of 25(OH)D, but the clinical significance of low 25(OH)D in this population remains unclear.