骨化三醇对大鼠局灶性脑缺血-再灌注神经保护作用的研究

目的探讨骨化三醇对大鼠局灶性脑缺血-再灌注模型的保护效应及其机制。方法将54只健康雄性成年SD大鼠随机分为三组:假手术组(8只)、骨化三醇干预组(23只,2μg.k-g1.d-1,持续8 d)和安慰剂组(23只,脂肪乳剂2m l.kg-1.d-1,持续8 d)。在第8天给药结束后1 h,以线栓法制作大鼠右侧大脑中动脉缺血后1 h再灌注模型,检测其3、6、9 h新皮质核转录因子(NF-κB)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10及72 h时脑梗死体积及神经细胞损伤情况。结果骨化三醇干预组与安慰剂组相比,脑缺血-再灌注后3、6、9 h的NF-κB活性、TNF-α含量亦显著降低(P<0.05),6 h的IL-10含量显著增加(P<0.05)。脑缺血-再灌注72 h骨化三醇组大鼠相对脑梗死体积为(11.8±3.6)%,明显小于安慰剂组的(21.6±4.2)%,P<0.05。结论骨化三醇可能通过对炎症介质的免疫调节减轻大鼠脑缺血-再灌注性损伤。     

骨化三醇治疗慢性肾病非透析患者继发性甲状旁腺功能亢进疗效观察

【目的】探讨骨化三醇治疗慢性肾病非透析患者继发性甲状旁腺功能亢进的疗效。【方法】以本院收治的37例合并继发性甲状旁腺功能亢进的慢性肾病非透析患者作为研究对象,根据患者血清全段甲状旁腺激素（iPTH）水平确定骨化三醇[1,25-（OH）2-D3]的给药剂量,对所有患者治疗前及治疗后第4、8和12周时的血钙（Ca）、血磷（P）,钙磷乘积（Ca＆#215;P）及血清iPTH水平进行监测,同时观察其不良反应发生情况。【结果】所有患者均顺利完成治疗及随访,无一例发生明显副反应。经治疗后,10例骨痛患者有8例骨痛消失,另2例骨痛改善不明显,6例皮肤瘙痒患者症状全部消失。血iPTH水平在治疗后4周、8周和12周呈持续下降趋势,与治疗前比较,差异均有统计学意义（P＜0．05）;而血Ca、血P和Ca＆#215;P与治疗前比较差异均无统计学意义（P＞0．05）。【结论】骨化三醇治疗慢性肾病非透析患者继发性甲状旁腺功能亢进疗效显著,不良反应轻,安全可靠。     

骨化三醇对MPTP诱导慢性帕金森病小鼠模型脑内神经递质的影响

目的探讨骨化三醇对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导慢性帕金森病小鼠模型脑内氨基酸类和单胺类神经递质的影响。方法C57BL／6小鼠随机分为对照组、模型组、骨化三醇高剂量给药组和低剂量给药组,构建MPTP慢性模型,应用高效液相色谱法测定中脑及纹状体内氨基酸类神经递质,包括天冬氨酸（Asp）、谷氨酸（Glu）、甘氨酸（Gly）、牛磺酸（Tau）、1,-氨基丁酸（GABA）和单胺类神经递质,包括多巴胺（DA）及其代谢产物3,4-双羟苯乙酸（DOPAC）的含量。结果与对照组相比,模型组小鼠氨基酸类神经递质除中脑内GABA外含量增加,纹状体内DA和DOPAC含量降低,代谢率增加俨〈O．01或P〈0．05）。骨化三醇给药组与模型组相比,高剂量可使中脑GIu,Gly,Tau及纹状体内五种氨基酸含量降低,DA和DOPAC含量增加,代谢率降低俨〈O．01或P〈0．05）;低剂量则仅可减缓中脑Tau和纹状体除Tau以外其他4种氨基酸含量增长状况。结论骨化三醇能改善MPTP所致慢性PD小鼠模型脑内神经递质含量异常,直接或间接保护DA能神经元,对其机制的深入研究有助于新型神经保护药物的开发。     

Effects of Postmenopausal Hormone Replacement Therapy With and Without Vitamin D3 on Circulating Levels of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D₃ on vitamin D metabolites (25OHD and 1,25(OH)₂D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D₃ group (vitamin D₃ 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D₃ group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March–April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D₃ group (33.5%, P < 0.001) and in the HRT + Vit D₃ group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1,25(OH)₂D) increased, however, only in the HRT group (23.7%, P < 0.05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D₃ supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D₃ did not increase serum calcitriol concentrations as much as HRT alone. Received: 14 June 1996 / Accepted: 17 June 1997     

Epidermal growth factor and calcitriol synergistically induce osteoblast maturation

Calcitriol (1,25(OH)₂D₃) plays a key role in the differentiation of osteoblasts, the cells responsible for the formation and maintenance of healthy bone matrix. Recently it has emerged that calcitriol influences the trafficking or stability of epidermal growth factor (EGF) receptors. However, how these agents might work together in regulating growth and differentiation has not been examined. Using the human osteoblast cell line, MG63, we were able to induce a profound differentiation response by treating these cells with a combination of calcitriol (100 nM) and EGF (10 ng/ml). Co-stimulation of MG63 osteoblasts with calcitriol and EGF led to synergistic increases in osteocalcin and alkaline phosphatase (ALP), proteins expressed by differentiating cells. Inhibition of differentiation was accomplished by MEK and protein kinase C (PKC) inhibitors. Other ligands known to signal via receptor tyrosine kinases could not substitute for EGF in the maturation response. These novel findings may help identify new processes that drive osteoblast differentiation.     

骨化三醇干预骨质疏松对高脂血症血管钙化的影响

目的探讨通过采用骨化三醇干预骨质疏松,对高脂血症导致的血管钙化的影响。方法选择2010年5月～2011年4月在我院进行治疗的高脂血症患者80例为研究对象,分为研究组和对照组各40例。对照组采用阿托伐他汀降血脂治疗,研究组在此基础上加用骨化三醇治疗。测定治疗前后两组颈动脉斑块的人数及斑块厚度、心脏瓣膜钙化的比例、肱动脉到胫后动脉的脉搏波速度。结果颈动脉钙化斑厚度研究组治疗后与治疗前比较差异显著（P〈0．05）,治疗后两组间比较差异具有统计学意义（P〈0．05）。踝臂脉搏波传导速度对照组与研究组治疗前后组内比较,差异均有统计学意义（P〈0．01）,研究组治疗后低于对照组（P〈0．01）。结论对高血脂合并骨质疏松症患者在降血脂治疗的基础上加用骨化三醇干预骨质疏松,能够改善血管钙化情况。     

骨化三醇对单侧输尿管梗阻大鼠肾小管上皮细胞转分化影响的研究

目的观察幼年大鼠单侧输尿管梗阻(UUO)肾组织中α-肌动蛋白(α-SMA)、E-钙黏蛋白(E-Cad)、转化生长因子-β1(TGF-β1)、骨形态发生蛋白-7(BMP-7)mRNA的表达,探讨骨化三醇对肾小管上皮细胞转分化(EMT)干预效应及机制。方法 54只雄性SD大鼠随机分为3组:假手术组(A组)、UUO模型组(B组)及UUO模型干预组(C组)各18只,灌胃满3、7、14d取肾。实时荧光定量聚合酶链反应(RT-PCR)法检测各组α-SMA、E-Cad、TGF-β1、BMP-7mRNA表达水平。结果与A组相比,B组E-Cad、BMP-7mRNA表达明显下降(P<0.01),α-SMA、TGF-β1mRNA表达显著增高(P<0.01);C组与B组相比,E-Cad、BMP-7mRNA表达明显上调(P<0.01),α-SMA、TGF-β1mRNA表达明显下降(P<0.01)。结论骨化三醇对UUO模型大鼠肾小管上皮细胞转分化有抑制作用,这种抑制作用可能与下调TGF-β的表达及上调BMP-7的表达有关。     

Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans

1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinson's disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.