Glucocorticoid receptor

对糖皮质激素的耐药性或敏感性被认为对儿童急性淋巴细胞白血病的疾病预后至关重要。泼尼松龙对耐药CCRF-CEM白血病细胞系具有延迟的双相作用，低剂量时坏死，高剂量时凋亡。在低剂量下，尽管泼尼松龙诱导了总细胞死亡，但它仍具有显性促有丝分裂作用，而在高剂量下，泼尼松隆的促有丝分化和细胞死亡作用得到了平衡。早期基因微阵列分析显示，40个基因存在显著差异。泼尼松龙的促有丝分裂/双相作用在耐药白血病细胞的情况下具有临床意义。这种方法可能会导致识别未来与糖皮质激素联合治疗中分子药物靶点的候选基因，以及糖皮质激素耐药性的早期标志物[1]。

一氧化氮被认为参与非特异性细胞免疫。革兰氏阴性细菌内毒素通过诱导一氧化氮合酶II（NOS II）增加吞噬细胞中活性氮中间体（RNI）的产生。抗炎糖皮质激素可减弱内毒素诱导的RNI增加。本研究评估了体内给予泼尼松龙对大肠杆菌脂多糖内毒素（LPS）诱导的大鼠血浆RNI和中性粒细胞NOS II mRNA增加以及RNI产生的影响。我们发现，静脉注射0.5mg/kg亚致死剂量的LPS后2小时内，LPS迅速诱导大鼠中性粒细胞中NOS II的mRNA和RNI（NO2-和NO3-阴离子）的产生。在LPS前15分钟给予药物剂量的泼尼松龙（50微克/kg，im），可减弱中性粒细胞产生NO2-和NO_3-，并抑制LPS刺激的NOS II mRNA。3-氨基-1,2,4-三嗪抑制NO2-和NO3-的产生，而不影响NOS II的基因表达。这些数据表明，LPS迅速诱导NOS II的功能基因表达，泼尼松龙通过抑制其mRNA的转录来阻止NOS II活性的诱导[2]。

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短期服用大剂量皮质类固醇后，膈肌萎缩和无力。在本研究中，研究了长期服用中等剂量的氟化和非氟化类固醇对大鼠膈肌收缩特性和组织病理学的影响。60只大鼠每天接受生理盐水、1.0 mg/kg曲安奈德或1.25或5 mg/kg泼尼松龙肌肉注射，持续4周。对照组和两个泼尼松龙组的呼吸和外周肌肉质量同样增加，而曲安奈德会导致严重的肌肉萎缩。对照组的最大强直张力平均为2.23+/-0.54kg/cm2（SD）。5-mg/kg泼尼松龙组膈肌束数量的增加产生了最大强直张力<2.0 kg/cm2（P<0.05）。此外，该组在力量频率方案期间的疲劳性最为明显（P<0.05）。相比之下，曲安奈德导致半松弛时间延长和力-频率曲线向左偏移（P<0.05）。对照组和1.25mg/kg泼尼松龙组的膈肌组织学检查显示正常模式。然而，在5-mg/kg泼尼松龙组中发现了肌源性变化，在曲安奈德组中更为明显。在后一组中发现了选择性IIb型纤维萎缩，但在泼尼松龙组中没有发现。总之，曲安奈德诱导IIb型纤维萎缩，导致呼吸肌力量减弱和力频曲线向左偏移。相比之下，5 mg/kg泼尼松龙引起膈肌收缩特性的改变和组织学变化，而没有纤维萎缩[3]。

泼尼松龙治疗[1]
根据1个月至12岁儿童静脉注射的平均体内剂量选择泼尼松龙的浓度（详细信息见补充数据，文件：CCRFCEM细胞毒性测定.xls）。此外，皮质醇当量的生物活性估计在40-200nM的范围内。为确保研究涵盖这些范围，将泼尼松龙稀释至以下12个浓度：对照组、10 nM、100 nM、1μM、5.5μM、11μM、22μM、44μM、88μM、175μM、350μM和700μM。

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细胞增殖测定 [1]
使用NIHON KOHDEN CellTaq-α血液分析仪测定细胞群计数。在开始接触Prednisolone/泼尼松龙后-24小时以及0小时、4小时、24小时、48小时和72小时对细胞进行计数。为此，从每个烧瓶中获得200μl细胞悬浮液，并直接用分析仪计数。

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蛋白质提取和蛋白质印迹[1]
在暴露于不同浓度的Prednisolone/泼尼松龙1小时和4小时后收获细胞。如前所述进行蛋白质提取和蛋白质印迹。以牛血清白蛋白为标准，采用Bradford法测定总蛋白含量。通过SDS-PAGE分离蛋白质，并用抗p65抗体进行蛋白质印迹

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微阵列分析[1]
cDNA微阵列芯片（1200个基因）从TAKARA（人癌症芯片v.40）获得。按照制造商的描述，使用CyScribe Post Labeling试剂盒进行杂交，使用Cy3和Cy5荧光染料。载玻片用微阵列扫描仪扫描。使用ScanArray微阵列采集软件生成图像。使用来自三个实验装置的cDNA，每个装置由三个独立的实验组成。实验装置由以下三对组成：对照组与10 nMPrednisolone（指定为0vs1），10 nM泼尼松龙与700μM泼尼松隆（指定为1vs3），对照组与700μM泼尼松松（指定为0vs3）。如前所述，这是一种“简单循环”实验设计，考虑了样本之间的所有可能组合。原始微阵列数据可作为补充数据。

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实时逆转录聚合酶链式反应（qRT-PCR）[1]
使用一步法Plexor™qRT-PCR试剂盒，在4小时和48小时的处理下，从3个样品对照中检测GRIM19（NDUFA13）基因，即10 nM和700μM的Prednisolone。该套引物是使用Promega的在线工具Plexor™引物设计系统v1.2设计的

Study design, animals, and treatment [3]
60 adult male Wistar rats, aged 14 wk, weighing 350-400 g, were randomized in quadruplets, into one of four treatment groups: control (C), saline, 0.05 ml/d i.m.; low dose prednisolone (LD), 1.25 mg/kg per d i.m.; high dose prednisolone (HD), 5 mg/kg per d i.m.; or triamcinolone-diacetate (TR), 1 mg/kg per d i.m. Dilution of medication was performed such that with each injection all animals received a similar volume (0.05 ml). During 4 wk the animals were injected daily in the left hindlimb. They were fed ad libitum and weighed twice weekly. After the treatment period, contractile properties, histological, and histochemical characteristics of the diaphragm were examined.[3]

rabbit LD50 intravenous 360 mg/kg Chemical and Pharmaceutical Bulletin., 22(1439), 1974 [PMID:4373183]

[1]. Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression. Leuk Res, 2009. 33(12): p. 1684-95.

[2]. Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone. Proc Soc Exp Biol Med. 1994 Mar;205(3):220-9.

[3]. Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently. J Clin Invest. 1993 Sep;92(3):1534-42.

Prednisolone sodium phosphate can cause developmental toxicity according to state or federal government labeling requirements.
Prednisolone sodium phosphate is an organic sodium salt of prednisolone phosphate. It is an ophthalmology drug used for the treatment of short-term inflammatory eye conditions and helps relieve inflammation, redness and irritation of the eyes. It has a role as an ophthalmology drug, an anti-inflammatory agent, a glucocorticoid receptor agonist, a prodrug and an anti-allergic agent. It is an organic sodium salt and a glucocorticoid. It contains a prednisolone phosphate(2-).
Prednisolone Sodium Phosphate is the sodium phosphate salt form of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. As a glucocorticoid receptor agonist, prednisolone sodium phosphate binds to specific intracellular glucocorticoid receptors, and causes the ligand- receptor complex to be translocated to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as various cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both potent mediators of inflammation. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cell populations.
See also: Prednisolone (has active moiety); Neomycin sulfate; prednisolone sodium phosphate (component of) ... View More ...

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In conclusion, this study shows: (a) prednisolone exerts a delayed biphasic effect on CCRF-CEM cells, necrotic at low doses and apoptotic at higher doses, (b) at low doses, prednisolone exerts a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone's mitogenic and cell death effects are counterbalanced. These mitogenic effects are of clinical importance in the case of resistant leukemic cells. It is of crucial importance if a certain administered dose of GCs to an ALL patient possesses proliferative rather than suppressive actions, (c) NF-κB is constitutively localized in the nucleus and its inhibition emerges as a possible candidate for the treatment of resistant leukemia, (d) prednisolone activates genes related to at least four different pathways upon 4 h treatment: apoptosis and tumor suppression, cell cycle progression, metabolism and intra- and extra-cellular signaling. Several of these genes manifested a biphasic differential expression profile. This approach might lead to the identification of genes candidates for future molecular drug targets in combination therapy with GCs. These drugs may affect the potential of GCs to inhibit growth of resistant leukemic cells. Also, this type of approach could identify potential early markers for GCs resistance. Early detection of resistance could facilitate the efficiency of ALL therapies.[1]

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In conclusion, the present study shows that triamcinolone and prednisolone have different effects on morphology and contractile properties of the rat diaphragm. Fluorinated steroids such as triamcinolone caused severe muscle wasting due to selective type Ilb fiber atrophy, resulting in markedly reduced respiratory muscle strength. Prednisolone in four times higher doses caused a tendency towards lower tetanic tensions and increased fatigability of diaphragmatic muscle bundles, with distinct alterations in muscle histology.[3]

C21H27NA2O8P

484.39

484.123

C, 52.07; H, 5.62; Na, 9.49; O, 26.42; P, 6.39

125-02-0

Prednisolone;50-24-8;Prednisolone hemisuccinate;2920-86-7;Prednisolone acetate;52-21-1; 630-67-1 (sodium metazoate); 72064-79-0 (valerate acetate); 125-02-0 (Na+ phosphate); 50-24-8 (free)

441409

White to light yellow solid powder

100 °C

361.9ºC

4.17E-21mmHg at 25°C

2.551

156.83

2

8

3

32

878

7

C[C@@]1([C@@]2(O)C(COP([O-])([O-])=O)=O)[C@](CC2)([H])[C@@](CCC3=CC4=O)([H])[C@]([C@]3(C=C4)C)([H])[C@@H](O)C1.[Na+].[Na+]

VJZLQIPZNBPASX-OJJGEMKLSA-L

InChI=1S/C21H29O8P.2Na/c1-19-7-5-13(22)9-12(19)3-4-14-15-6-8-21(25,17(24)11-29-30(26,27)28)20(15,2)10-16(23)18(14)19;;/h5,7,9,14-16,18,23,25H,3-4,6,8,10-11H2,1-2H3,(H2,26,27,28);;/q;2*+1/p-2/t14-,15-,16-,18+,19-,20-,21-;;/m0../s1

disodium;[2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] phosphate

prednisolone; Prednisolone Phosphate Sodium; prednisolone sodium phosphate; 125-02-0; Prednisolone phosphate sodium; Phortisolone; Metreton; Orapred; Predair; Pediapred; AKOS016010152; AK115681; sodium phosphate Predsol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~50 mg/mL (~103.2 mM)

配方 1 中的溶解度: 100 mg/mL (206.45 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。