1,25-二羟维生素D3对OS-732人成骨样细胞增殖与分化的影响

目的观察1,25-二羟维生素D3对体外培养的人成骨样细胞增殖与分化的影响,以进一步探讨其治疗骨质疏松的机制。方法采用MTT比色分析法检测1,25-二羟维生素D3对体外培养OS—732人成骨样细胞增殖的作用与效价。采用培养细胞匀浆上清测单位蛋白下的碱性磷酸酶活性,培养基中骨钙素(BGP)含量分析方法检测1,25-二羟维生素D3对OS—732人成骨样细胞分化的影响。结果培养第4天,10-7mol/L1,25-二羟维生素D3显著抑制成骨样细胞增殖(P<0.05),10-8mol/L、10-9mol/L1,25-二羟维生素D3对成骨样细胞的作用不明显。培养4天后培养基中BGP水平在10-7mol/L组变化不大,在10-8mol、10-9mol/L1,25-二羟维生素D3组BGP水平显著增高(P<0.05,P<0.01)。结论1,25-二羟维生素D3抑制成骨样细胞增殖在高剂量时作用显著,促进成骨样细胞分化作用在较低剂量显著。     

1,25-二羟维生素D3对OS-732人成骨样细胞增殖与分化的影响

目的观察1,25-二羟维生素D3对体外培养的人成骨样细胞增殖与分化的影响,以进一步探讨其治疗骨质疏松的机制.方法采用MTT比色分析法检测1,25-二羟维生素D3对体外培养OS-732人成骨样细胞增殖的作用与效价.采用培养细胞匀浆上清测单位蛋白下的碱性磷酸酶活性,培养基中骨钙素(BGP)含量分析方法检测1,25-二羟维生素D3对OS-732人成骨样细胞分化的影响.结果培养第4天,10-7mol/L1,25-二羟维生素D3显著抑制成骨样细胞增殖(P＜0.05),10-8mol/L、10-9mol/L1,25-二羟维生素D3对成骨样细胞的作用不明显.培养4天后培养基中BGP水平在10-7mol/L组变化不大,在10-8mol、10-9mol/L1,25-二羟维生素D3组BGP水平显著增高(P＜0.05,P＜0.01).结论1,25-二羟维生素D3抑制成骨样细胞增殖在高剂量时作用显著,促进成骨样细胞分化作用在较低剂量显著.     

血清1,25-二羟维生素D3表达水平对糖尿病患者的临床意义

目的 观察糖尿病患者血清中1,25-二羟维生素D3的表达水平,探讨其表达水平对糖尿病患者的临床意义.方法 收集本院单纯糖尿病患者48例作为单纯糖尿病组,糖尿病肾病患者37例作为糖尿病肾病组,对照组选取50例健康体检者,采用ELISA法检测患者血清中1,25-二羟维生素D3的表达水平,分析1,25-二羟维生素D3的表达水平与糖尿病患者病情严重程度的关系.结果 单纯糖尿病及糖尿病肾病患者血清中1,25-二羟维生素D3及25-二羟维生素D3表达水平明显低于健康体检者（t=4.87,P＜0.05;t=5.12,P＜0.05）;糖尿病肾病组患者血清中1,25-二羟维生素D3及25-二羟维生素D3的表达水平明显低于单纯糖尿病组,差异有统计学意义（t=3.56,P＜0.05）.结论 糖尿病患者血清中1,25-二羟维生素D3的表达水平低于健康人,其表达水平与糖尿病患者病情严重程度呈负相关,这可能有助于临床上对糖尿病患者早期病情的判断。     

1,25-二羟维生素D_3联合缬沙坦减少IgA肾病尿蛋白的疗效观察

目的观察1,25-二羟维生素D3(VD3)联合缬沙坦减少IgA肾病尿蛋白的疗效。方法将60例肾活检明确诊断为IgA肾病的患者采用随机数字表法分为ARB组和ARB+VD3组,ARB+VD组根据所应用的1,25-二羟维生素D3的剂量分为联合治疗组1和组2,观察6个月,治疗过程中监测血压,检测治疗前后尿蛋白、肾功能、血钙、血钾水平。结果治疗后3组尿蛋白均较基线下降,差异有统计学意义(P<0.05),且3组之间尿蛋白的下降程度两两比较,各组差异有统计学意义(P<0.05),联合治疗组2下降最为显著,无明显不良反应。结论 1,25-二羟维生素D3联合缬沙坦对减少IgA肾病尿蛋白有较好的疗效,联合较大剂量1,25-二羟维生素D3效果更为显著,为IgA肾病的初始治疗提供更优先的方案。     

1,25-(OH)2D3在临床的应用

维生素D3是一些抗佝偻病物质的总称,其活性代谢物主要包括25-羟维生素D3(25-(OH)D3)、24,25-二羟维生素D3(24,25-(OH)2D3)和1,25-二羟维生素D3(1,25-(OH)2D3),其中生物活性最强的代谢物是1,25-(OH)2D3.1,25-(OH)2D3是维生素D经肝、肾代谢后的活性形式,它不仅参与内分泌系统对骨和无机盐的代谢调节,还参与调节许多细胞的代谢过程.     

1,25-二羟维生素D_3对人胃腺癌细胞诱导分化的实验研究

目的观察1,25-二羟维生素D3对胃腺癌MGC-803细胞的诱导分化作用。方法1,25-二羟维生素D3(10-6、10-5、10-4mmol.L-1)作用于MGC-803细胞后,应用四甲基偶氮唑蓝(MTT)法测定细胞增殖能力、平板克隆试验测定细胞集落形成率、流式细胞仪测定细胞周期、TRAP-银染法测定端粒酶活性。结果1,25-二羟维生素D3作用24、48、72和96h后胃腺癌细胞生长均明显受抑制,48h后细胞周期出现向G0/G1期移行的特征性动力学改变,端粒酶活性明显受到抑制。细胞集落形成率明显下降(P<0.05)。结论1,25-二羟维生素D3对人胃腺癌细胞有诱导分化作用。     

秦皇岛地区婴幼儿血清25羟维生素D水平

维生素D分为膳食维生素D和阳光维生素D。无论是阳光维生素D还是膳食维生素D,都在肝脏由25α-羟化酶催化,完成第一次羟化成为25羟维生素D;在肾脏或其他靶组织、细胞由1-α羟化酶催化,完成第二次羟化,生成1,25-二羟维生素D。1,25-二羟维生素D是活性维生素D。血清25羟维生素D     

1，25二羟维生素 D3诱导喉癌细胞 Hep-2细胞凋亡及其对Bax／Bcl-2蛋白表达水平的影响

目的：研究1,25二羟维生素 D3抑制人喉癌 Hep-2细胞增殖作用,诱导细胞凋亡及其凋亡相关机制。方法用不同剂量（10－8、10－7、10－6 mol／L）1,25二羟维生素 D3处理 Hep-2细胞24 h、48 h、72 h,四甲基偶氮唑蓝法（MTT）检测 Hep-2细胞的增殖情况,计算抑制率。流式细胞术检测 Hep-2细胞的凋亡率。Western blot 检测用药前后细胞中 Bax 和 Bcl-2蛋白的表达水平。结果1,25二羟维生素 D3可以抑制 Hep-2细胞增殖（P ＜0．05）,最高抑制率可达30．71％,在上述浓度内随着浓度增加、时间延长抑制作用逐渐增强,呈时间－剂量依赖性。10－7、10－6 mol／L 1,25二羟维生素 D3作用48 h 后,Hep-2凋亡细胞比例显著增加,凋亡率高于空白对照组（P ＜0．05）。1,25二羟维生素 D3处理48 h 后,Hep-2细胞 Bax 蛋白表达上升,Bcl-2蛋白表达水平下降。结论在一定浓度范围内1,25二羟维生素 D3能够抑制人喉癌 Hep-2细胞的增殖,呈时间－剂量依赖性,其抑制作用与诱导细胞凋亡有关;1,25二羟维生素 D3可通过上调 Bax 蛋白表达、下调 Bcl-2蛋白表达诱导 Hep-2细胞凋亡。     

喘息患儿血清1,25-二羟维生素D_3和总IgE的变化及孟鲁司特的干预研究

目的：探讨血清1,25-二羟维生素D3和总免疫球蛋白E（Ig E）在喘息患儿体内的含量变化,以及孟鲁司特对两种物质的干预作用。方法：选取我院收治的60例6个月~3岁的喘息患儿,分为非干预组和孟鲁司特干预组各30例,同时选取同年龄段的健康体检儿童30例作为对照组。采用放射免疫法测定血清1,25-二羟维生素D3,酶联免疫法测定血清总Ig E水平,观察三组儿童血清1,25-二羟维生素D3和Ig E的差异,以及喘息患儿治疗前后两种物质的变化,并比较非干预组和孟鲁司特干预组的临床疗效。结果：喘息患儿血清1,25-二羟维生素D3明显低于健康儿童（P〈0.05）,血清总Ig E水平明显高于健康儿童（P〈0.05）,孟鲁司特干预组临床疗效优于非干预组（P〈0.01）,孟鲁司特可以降低喘息患儿血清总Ig E水平（t=22.496,P〈0.01）。结论：1,25-二羟维生素D3和血清总Ig E均参与喘息患儿的免疫调节机制,孟鲁司特是治疗喘息患儿一种安全有效的药物,并且通过降低血清总Ig E减轻过敏性喘息。     

1,25-二羟维生素D3对哮喘大鼠维生素D3上调蛋白1的影响

目的探讨1,25-二羟维生素D3(1,25(OH)2D3)对哮喘大鼠维生素D3上调蛋白l(VDUP1)的表达及气道炎症的影响.方法28只Wistar大鼠随机分为四组:对照组、哮喘组、1,25-(OH)2D3组和地塞米松组.以卵蛋白为致敏原制备哮喘大鼠模型,1,25-(OH)2D3组在激发前1h口服1,25-(OH)2D...     

1,25-二羟基维生素D_3对环磷酰胺处理的NOD小鼠糖尿病的影响

目的　探讨 1,2 5 -二羟基维生素 D3 对环磷酰胺促发的 NOD鼠 1型糖尿病的预防作用。方法　N OD鼠从离乳后隔日接受 1,2 5 -二羟基维生素 D3 治疗 ,第 10周龄给予环磷酰胺 30 0 m g/ kg,观察 1,2 5 -二羟基维生素 D3 对环磷酰胺处理的 NOD鼠糖尿病发病率和胰岛炎的影响 ,及对 Th1、Th2细胞因子 m RNA表达的影响。结果　 1,2 5 -二羟基维生素 D3 处理组糖尿病发病率为 17% ,明显低于对照组 6 7% (P<0 .0 5 ) ,且胰岛炎严重程度也明显减轻。处理组胰腺 TNT- α、IFN- γ m RNA的表达较对照组明显降低 ,而 IL- 10 m RNA的表达无明显改变。结论　 1,2 5 -二羟基维生素 D3 可以预防 NOD鼠环磷酰胺诱发的糖尿病的发生 ,其机制可能与纠正 Th1型细胞因子与 Th2型细胞因子比例失衡有关     

1,25-Dihydroxyvitamin-D3 treatment reduces cardiac hypertrophy and left ventricular diameter in spontaneously hypertensive heart failure-prone (cp/+) rats independent of changes in serum leptin

A number of investigators have observed insufficient 25-hydroxyvitamin D status in patients with congestive heart failure, suggesting a role for vitamin D insufficiency in the pathogenesis of this disorder. We have observed cardiac hypertrophy and collagen accumulation in rats deficient in vitamin D and in the hearts of vitamin D-receptor knockout mice. Our studies indicate that absence of vitamin D-mediated signal transduction and genomic activation results in cardiomyocytes overstimulation including increased contractility. These events ultimately lead to cardiomyocyte hypertrophy. In this report, we used spontaneously hypertensive heart failure rats cp/+ (hemyzygous for the corpulent gene, a mutant isoform of the leptin receptor) fed a normal and a high-salt diet to assess the potential for activated vitamin D (1,25 dihydroxyvitamin D3) to prevent cardiac hypertrophy and increases in cardiac output. After 13 weeks, as compared with untreated rats, we observed that 1,25 dihydroxyvitamin D3 treatment in rats fed a high-salt diet resulted in lower heart weight, myocardial collagen levels, left ventricular diameter, and cardiac output despite higher serum leptin levels. These studies suggest that 1,25(OH)2D3 treatment may prevent the development of cardiac hypertrophy, an important contributing factor in the progression of congestive heart failure.     

Involvement of PI3-K in neuroprotective effects of the 1,25-dihydroxyvitamin D3 analogue - PRI-2191

The active form of 1,25-dihydroxyvitamin D(3) prevents neuronal damage in vitro and in vivo , however, it induces also hypercalcemia and hyperphosphatemia. Side-chain-modified analogues of 1,25-dihydroxyvitamin D(3), which show low calcemic activity, may be potentially useful in the treatment of some neurodegenerative diseases. Previously, we have found that PRI-2191 more potently than 1,25-dihydroxyvitamin D(3) protects human neuroblastoma (SH-SY5Y) cells against hydrogen-peroxide-induced toxicity. In the present study, we evaluated effects of two other 1,25-dihydroxyvitamin D(3) analogues - PRI-1890 and PRI-1901 on the neuronal degeneration in the same cell model. In line with the previous study, 24-h incubation with hydrogen peroxide (0.5 mM) was toxic to cells, as evidenced by an enhanced efflux of lactate dehydrogenase into the culture medium, and these effects were prevented by PRI-1890 and PRI-1901 at concentration of 5, 50 and 500 nM. Comparing the neuroprotective effects of secosteroids, we found that all three analogues were efficient at lower concentration than 1,25-dihydroxyvitamin D(3) and among them the PRI-2191 showed the most evident concentration-dependent effect. In the second part of this study, an involvement of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K), kinases which play a crucial role in neurodegenerative processes, in neuroprotective action of 1,25 dihydroxyvitamin D(3) and its the most potent analogue PRI-2191 has been investigated. The inhibitor of c-Jun N-terminal kinase (JNK)-MAPK (SP600125, 1 microM), inhibitor of p38-MAPK (SB-203580, 1 and 10 microM) and inhibitor of extracellular signal-regulated kinase (ERK)-MAPK (PD-98059, 15 and 30 microM) attenuated the hydrogen peroxide-induced toxicity. Moreover, PD-98059 (30 microM) enhanced neuroprotective effects of 1,25 dihydroxyvitamin D(3) but not that of PRI-2191. In contrast, the inhibitor of PI3-K (wortmannin, 10, 100 nM) did not affect hydrogen peroxide-induced cell damage itself, however, it significantly antagonized the effect of PRI-2191. On the other hand, wortmannin did not affect the neuroprotective effects of 1,25 dihydroxyvitamin D(3) This suggests that the activation of PI3-K/Akt signaling pathway plays an important role in the mechanism of inhibitory action of PRI-2191 on hydrogen peroxide-evoked toxicity in SH-SY5Y cells. Furthermore, these data point to differential involvement of ERK-MAPK and PI3-K in neuroprotective effects of 1,25 dihydroxyvitamin D(3) and its low-calcemic analogue - PRI-2191.     

Synthesis of diacetoxy acetal derivatives of santonin and their enhancing effects on HL-60 leukemia cell differentiation

Several diacetoxy acetal analogues have been synthesized from santonin and assessed for their ability of inducing or enhancing the differentiation of human HL-60 leukemia cells. The compounds themselves had little effect on HL-60 cell differentiation. However, three analogues, 2a, 3a, and 5b, synergistically enhanced 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced HL-60 cell differentiation when combined with 5 nM of dihydroxyvitamin D3 [1,25-(OH)2D3], a well-known differentiation inducer. Especially, the compound 5b profoundly enhanced the 1,25-(OH)2D3]-induced HL-60 cell differentiation.     

188Re标记叶酸偶联白蛋白纳米微球对SKOV3人卵巢癌生长抑制作用研究

【摘要】目的观察核素标记叶酸靶向白蛋白纳米微球(¹⁸⁸Re -folate-CDDP/HAS MNP)对SKOV₃人卵巢癌细胞生长作用的影响。方法建立人卵巢癌细胞SKOV3裸鼠模型,并将64只荷瘤鼠随机分成8组,每组8只,分别为（A）阴性对照组;（B）采用CDDP方案化疗的单纯化疗组;（C）核素靶向内照射的单纯放疗组;（D）磁感应热疗的单纯热疗组;（E）化疗联合放疗组;（F）化疗联合热疗治疗组;(G)放疗联合热疗治疗组;(H)热疗、化疗、放疗联合治疗组。各组经治疗后,观察肿瘤生长增殖情况,计算肿瘤质量抑制率,观察肿瘤组织病理变化。结果各治疗组的肿瘤质量均低于对照组（P<0.05）,且与其他治疗组相比,热疗、化疗、放疗联合治疗组的肿瘤质量最低（P<0.05）。结论磁感应热疗、化疗、核素靶向内照射放疗的联合作用能有效抑制卵巢癌的生长,对卵巢癌治疗具有潜在应用前景。     

Minimizing bone abnormalities in children with renal failure

Renal osteodystrophy (ROD), a metabolic bone disease accompanying chronic renal failure (CRF), is a major clinical problem in pediatric nephrology. Growing and rapidly remodeling skeletal systems are particularly susceptible to the metabolic and endocrine disturbances in CRF. The pathogenesis of ROD is complex and multifactorial. Hypocalcemia, phosphate retention, and low levels of 1,25 dihydroxyvitamin D(3) related to CRF result in disturbances of bone metabolism and ROD. Delayed diagnosis and treatment of bone lesions might result in severe disability.Based on microscopic findings, renal bone disease is classified into two main categories: high- and low-turnover bone disease. High-turnover bone disease is associated with moderate and severe hyperparathyroidism. Low-turnover bone disease includes osteomalacia and adynamic bone disease.The treatment of ROD involves controlling serum calcium and phosphate levels, and preventing parathyroid gland hyperplasia and extraskeletal calcifications. Serum calcium and phosphorus levels should be kept within the normal range. The calcium-phosphorus product has to be <5 mmol(2)/L(2) (60 mg(2)/dL(2)). Parathyroid hormone (PTH) levels in children with CRF should be within the normal range, but in children with end-stage renal disease PTH levels should be two to three times the upper limit of the normal range. Drug treatment includes intestinal phosphate binding agents and active vitamin D metabolites. Phosphate binders should be administered with each meal. Calcium carbonate is the most widely used intestinal phosphate binder. In children with hypercalcemic episodes, sevelamer, a synthetic phosphate binder, should be introduced. In children with CRF, ergocalciferol (vitamin D(2)), colecalciferol (vitamin D(3)), and calcifediol (25-hydroxyvitamin D(3)) should be used as vitamin D analogs. In children undergoing dialysis, active vitamin D metabolites alfacalcidol (1alpha-hydroxy-vitamin D(3)) and calcitriol (1,25 dihydroxyvitamin D(3)) are applied. In recent years, a number of new drugs have emerged that hold promise for a more effective treatment of bone lesions in CRF. This review describes the current approach to the diagnosis and treament of ROD.     

Cinacalcet HCl: a novel therapeutic for hyperparathyroidism

Hyperparathyroidism (HPT) is a significant clinical concern for patients with a variety of diseases, notably the secondary HPT associated with chronic kidney disease requiring dialysis. Secondary HPT is associated with elevated para-thyroid hormone (PTH) levels, decreased levels of 1,25 dihydroxyvitamin D, and disordered mineral levels (usually high calcium and phosphorus). If not controlled, secondary HPT can result in bone disease, vascular calcification, and ultimately, patient mortality. Established, conventional therapies, such as 1,25dihydroxyvitamin D analogues (vitamin D analogues) and phosphate binders, have proven to be inadequate in enabling patients to meet the National Kidney Foundation's-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) treatment goals for PTH, calcium and phosphorus levels. A novel therapeutic, cinacalcet HCl (formerly AMG 073; Sensipar in the US and Mimpara in Europe; Amgen, Inc.), binds directly to the calcium-sensing receptor (CaR) on the cells of the parathyroid gland, increasing the receptor's sensitivity to calcium and reducing PTH, serum calcium and phosphorus levels. Treatment with cinacalcet in clinical trials has safely and effectively improved achievement of the NKF-K/DOQI goals. Cinacalcet has also reduced serum calcium levels in patients with primary HPT, including parathyroid carcinoma, in the clinical trial setting. Evidence suggesting the utility of cinacalcet in these diseases and the potential for additional therapeutic applications will be discussed.     

自制抑瘤汤结合放化疗对肿瘤的疗效分析

目的对放疗化疗的肿瘤患者结合自制抑瘤汤辅助治疗,探讨抑瘤汤作用的情况。方法分为放疗、化疗、放疗结合抑瘤汤、化疗结合抑瘤汤,对照观察抑瘤汤的作用。结论抑瘤汤能明显改善放化疗的预后情况。