活性维生素D3的免疫调节作用

活性维生素 D3[1,25(OH)2VitD3]对钙磷代谢有重要的调节作用.近年来,大量体外实验和临床研究发现,活性维生素D3有重要的抗炎和免疫调节作用.此文就活性维生素D3对免疫系统和免疫相关疾病的调节作用作一系统性总结.     

骨化三醇的免疫调节作用

骨化三醇在调节钙、磷代谢的同时还有对免疫系统的广泛作用，这一特性正从实验动物阶段向临床应用过渡。本文就其对免疫细胞、细胞因子、免疫应答的调节及与环孢素的协同作用作一综述。     

维生素D在神经系统中的作用研究进展

维生素D主要包括维生素D2(麦角骨化醇)和维生素D3胆骨化醇。人体内维生素D主要来源是紫外线照射皮肤,由皮肤基底层的7-脱氢胆骨化醇转化为胆骨化醇,也可以通过食物获取一部分。其生化作用通过肝脏和肾脏羟化形成活性代谢产物1,25二羟基维生素D3[1,25(OH)2D3]实现。     

钒联合维生素D3对结肠癌荷瘤裸鼠的治疗作用

目的 探讨钒联合维生素D3(VitD3)对结肠癌的治疗作用.方法 100只裸鼠皮下接种HCT116结肠癌细胞,成瘤后原位移植.建立结肠癌裸鼠模型后随机等分为钒(A)组、Vit D3(B)组、钒联合VitD3(C)组和对照(D)组.用药4周后,每组取18只脱颈处死,检测肿瘤体积和转移灶数节,免疫组化检测瘤体增殖细胞核抗原(PCNA)指数,其余裸鼠用于生存试验,流式细胞仪检测肿瘤细胞凋亡和细胞周期.结果 故 C组裸鼠增殖指数显著低于D组(P<0.05),荷瘤裸鼠生存时间显著延长(P<0.05),肿瘤细胞凋亡增加(P<0.05),细胞停留在G0/G1期.结论 钒联合Vit D3具有明显的抗结肠癌细胞增殖、诱导细胞凋亡的作用.     

1,25-(OH)_2D3的免疫调节特性及对相关疾病的作用

1,25-(OH)2D3(骨化三醇)是维生素D的衍生物,具有广泛的生物活性。此文主要从其对免疫细胞生物学效应及免疫相关疾病的可能治疗机制和副作用等方面做一综述。     

骨化三醇的免疫调节作用

以往认为食物 (鱼肝 ,牛奶 )及表皮中的 7 脱氢胆固醇经太阳光照射异构形成维生素Ｄ3 ,在肝脏经 2 5羟化酶生成 2 5羟维生素Ｄ3 后 ,肾线粒体的细胞色素Ｄ 45 0对其分子中的1 ａ作用是生成骨化三醇 (ｃａｌｃｉｔｒｏｌ,1,2 5 二羟维生素Ｄ3 )的经典途径。近来的研究表明 ,除肾脏外 ,胎盘 ,免疫细胞 (如激活的Ｔ细胞及Ｔ细胞系列 ,巨噬细胞等 )也可异位合成 1ａ羟化酶 ,如感染和异体反应。实验证实了骨化三醇除调节体内的钙、磷代谢外 ,对免疫系统也有广泛的作用[1] 。骨化三醇是通过结合靶细胞 [单核细胞及活化的淋巴细胞 (Ｔ淋巴细胞 ,Ｂ…     

活性维生素D3治疗老年骨质疏松症

目的：观察活性维生素D3（阿法骨化醇胶丸1α-oH-D3)在治疗老年骨质疏松症的疗效。方法：选择30例60岁以上老年骨质疏松症患者,口服活性维生素D30.5ug每日一次,共30d为一疗程,同时适量补充钙剂,在服药前,服药后2周,4周分别进行腰背痛,膝关节痛及日常活动能力评分观察疗效。计算有效率。结果：腰背痛及下肢痛缓解有效率70%,日常活动功能改善有效率66.7%,仅有2例患者有轻度胃肠道反应,口服胃肠动力药物后不影响继续服药。结论：活性维生素D3是治疗老年骨质疏松症安全有效的药物。对改善老年骨质疏松患者日常活动能力及缓解腰背及下肢痛有明显疗效。     

1,25-二羟基维生素D3与系统性红斑狼疮的关系研究

维生素D由皮肤中的胆固醇合成,然后代谢为肝、肾及外周免疫炎症细胞中的活性维生素D.有关研究表明,维生素D与多种自身免疫性疾病的发展呈负相关(如甲状腺毒症、虹膜睫状体炎、克罗恩病、溃疡性结肠炎、寻常型牛皮癣、风湿性多肌痛等),因此,该文就维生素D在系统性红斑狼疮的发病机制中的作用及治疗性补充剂的有效性相关研究进展进行了综...     

活性维生素D_3 顺铂对卵巢癌HO-8910细胞株的凋亡研究

目的观察1,25(OH)2维生素D3单独及其与顺铂合用对人卵巢癌细胞株凋亡的影响及Bax蛋白的表达情况。方法四甲基偶氮唑蓝(MTT)法检测细胞抑制率,流式细胞术测定细胞周期及凋亡率,免疫组织化学法检测Bax蛋白表达情况。结果1,25(OH)2维生素3、顺铂均可抑制HO-8910细胞的生长(P<0.01)、均可阻滞细胞于G0/G1期并诱导HO-8910细胞凋亡(P<0.01),当两者合用时上述作用加强,凋亡率明显上升(P<0.01),两者均可上调Bax蛋白表达(P<0.01),两者合用时Bax蛋白表达增强(P<0.01)。结论1,25(OH)2维生素D3与顺铂合用能协同抑制HO-8910细胞的生长并进一步诱导其凋亡。     

维生素D与2型糖尿病的相关性研究进展

近年研究显示,截至2008年全球已有10亿人存在维生素D(vitamin D)缺乏或不足[1],维生素D缺乏症已成为公共健康问题。研究表明,除调节钙、磷代谢,维持骨的矿化外,维生素D的生物学作用已经超出传统范围,与心血管疾病、代谢综合征、肿瘤、2型糖尿病(T2DM)和免疫应答等均有关[2-4]。     

遵义地区人群维生素D受体基因外显子2多态性

目的探讨遵义地区人群维生素D受体（VDR）基因第2外显子（起始密码子,e2）的单核苷酸多态性分布情况。方法收集110例遵义地区汉族人群静脉血标本,采用聚合酶链反应．限制性片段长度多态性法测定VDR基因e2序列多态性．分析该人群中基因型频率和基因频率分布规律。结果FokI的等位基因频率为F0．741、f0．259。结论VDR基因e2序列在遵义地区汉族中的分布具有多态性。     

维生素D受体对心肌缺血再灌注损伤的影响及作用机制

目的 探讨维生素D受体(vitamin D receptor,VDR)对心肌缺血再灌注损伤的影响及作用机制.方法 2018年12月至2019年1月,选择野生型雄性C57BL/6小鼠60只作为研究对象,构建小鼠心肌缺血再灌注损伤模型,并将小鼠按照随机数字表法进行分组,分为假手术组、Vehicle组、Calcitriol组...     

Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases

The active form of vitamin D, 1,25-Dihydroxyvitamin D3 [l,25(OH)2D3], is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and retinoic acid. VDR ligands regulate calcium and bone metabolism, control cell proliferation and differentiation, and exert immunoregulatory activities. The immunoregulatory properties of VDR ligands are currently exploited clinically for the topical treatment of psoriasis, a Th1 cell-mediated autoimmune disease of the skin, but recent advances in understanding their functions and novel insights into the immunomodulatory mechanisms they control suggest a wider applicability in the treatment of autoimmune diseases. In addition to direct effects on T cell activation, VDR ligands modulate with different mechanisms the phenotype and function of antigen-presenting cells (APCs), and, in particular, of dendritic cells (DCs). In vitro and in vivo experiments have shown that VDR ligands induce DCs to acquire tolerogenic properties that favor the induction of regulatory rather than effector T cells. These intriguing actions of VDR ligands have been demonstrated in several experimental models and could be exploited, in principle, to treat a variety of human autoimmune diseases.     

Vitamin D,vitamin D analogs (deltanoids) and prostate cancer

‘Vitamin D’ is a generic term for a family of secosteroids, members of which bind to the vitamin D receptor. Calcitriol, the active form of vitamin D, has antiproliferative effects on many tumor cells. However, clinical use of calcitriol in cancer prevention or therapy is limited because it induces hypercalcemia at the necessary supraphysiological doses. The anti-tumor effects of vitamin D analogs (deltanoids) have been researched extensively; more than 3000 deltanoids have now been described. Prostate cancer is more common in northern geographic regions; mortality decreases with exposure to sunlight. As UV light is necessary for vitamin D synthesis in the skin, it has long been dogma that vitamin D is involved. This review concerns deltanoids that have been assessed for use in treating or preventing prostate cancer.     

荆芥穗多糖的免疫调节活性

目的 研究荆芥穗多糖(HSP)对Raw264.7细胞和免疫抑制小鼠的免疫调节活性.方法 通过水提醇沉法提取HSP,苯酚-硫酸法测定HSP的总糖含量,硫酸-四硼酸钠法测定糖醛酸含量,考马斯亮蓝染色法测定蛋白质含量,高效液相色谱(HPLC)分析单糖组成;体外分别采用噻唑蓝(MTT)法和流式细胞术检测HSP对Raw264.7...     

活性维生素D3类药物研究概况

活性维生素D3除了具有调节钙磷代谢的功能外,还是一种细胞循环调节剂,影响细胞的增殖、分化和凋亡.活性维生素D3配体,通过与维生素D受体结合,在体内发挥多种多样的生理学功能,临床上可用来治疗炎症、皮肤病、骨质疏松、癌症和免疫疾病等.为了减少钙血症等不良反应,并使活性维生素D3的各种生理学作用相分离,到目前为止已经合成出3000余个活性维生素D3衍生物.该文对活性维生素D3的临床应用、构效关系及其研究最新进展进行综述.     

缺乏维生素D受体激活及CYP27B1代谢调控在心肾综合征中的作用

近年来研究发现,缺乏维生素D受体（VDR）激活与心肾综合征的发生发展关系密切。循环血液中90%以上的活性维生素D,即1,25（OH）2D3必须经由肾脏25-羟基维生素D-1α-羟化酶（CYP27B1）的羟化作用产生,从而发挥生物学效应。心肾综合征时,CYP27B1酶受损,循环内分泌1,25（OH）2D3生成不足,其与心脏和肾脏VDR结合减少,从而加重心肾损伤。因此,CYP27B1和VDR可能成为联系肾脏病和心血管疾病的重要靶标。本文就维生素D/VDR和CYP27B1的代谢调控在心肾综合征中的作用进行综述,以期为心肾综合征的治疗提供新的思路。     

Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (tacalcitol)

1. The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1α,24(R)-dihydroxyvitamin D₃) were studied using an enzyme-linked immunosorbent assay.
2. In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-α alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10⁻¹² M and 10⁻⁷ M.
3. When the cells were treated with TNF-α and IFN-γ in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-α-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-α-treated cells. On the other hand, RANTES production was enhanced by 10⁻¹¹ M and 10⁻¹⁰ M of tacalcitol, and dose-dependently suppressed by tacalcitol concentrations higher than 10⁻⁹ M.
4. Active vitamin D₃ compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D₃ compounds, tacalcitol, 1α,25-dihydroxyvitamin D₃ and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D₃ compounds. Cyclosporin A significantly stimulated RANTES production at 10⁻⁶ M and IL-8 production at 10⁻⁷ M and 10⁻⁶ M.
5. The results of this study suggest that active vitamin D₃ compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts.

     

Anti-tumor effects of 1,25-dihydroxyvitamin D3 and vitamin D analogs

The role of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) as a regulator of cell growth and differentiation is well recognized. Currently, 1, 25-(OH)2D3 and vitamin D analogs are being evaluated for their therapeutic potential in the treatment of hyperproliferative disorders like cancer. In the present review, we will discuss several processes that might be involved in 1,25-(OH)2D3- and vitamin D analog-mediated suppression of cancer cell growth. The effects on tumor cell proliferation, differentiation, apoptosis, angiogenesis, metastases, and parathyroid hormone-related peptide secretion will be highlighted. In addition, combination therapy with other tumor effec tive drugs will be addressed. Furtermore, we will focus on the potential drawbacks and the possible side effects of vitamin D compounds in the treatment of cancer.