HMG-CoA reductase

阿托伐他汀治疗通过下调心肌梗死期间心肌细胞中 GRP78、caspase-12 和 CHOP 的表达，降低心肌细胞凋亡。此外，它还刺激内质网 (ER) 以应对心力衰竭和血管紧张素 II (Ang II) 刺激。 ） 紧张。 4]。

阿托伐他汀治疗（20-30 mg/kg；口服强饲；每天一次；持续 28 天；ApoE−/− 小鼠）显着减少凋亡细胞、内质网 (ER) 应激信号蛋白以及 Caspase12 和 Caspase12 激活的数量。 ApoE-/- 小鼠中的 Bax 由 Ang II 触发。阿托伐他汀治疗后，促炎细胞因子如 IL-6、IL-8 和 IL-1β 被显着抑制 [5]。

在制造商推荐的条件下，使用来自Sigma-Aldrich（St.Louis，MO，USA）的具有人酶催化结构域（在大肠杆菌中表达的重组GST融合蛋白）的HMG-CoA还原酶测定试剂盒来鉴定植物提取物的最有效部分。纯化的人酶储备溶液（Sigma）的浓度为0.52–0.85 mg蛋白质/mL。使用参考他汀类药物普伐他汀（来自Sigma）作为阳性对照。为了在规定的测定条件下表征HMG-CoA还原酶的抑制作用，含有4 μL NADPH（以获得400的最终浓度 μM）和12 μL HMG-CoA底物（以获得400的最终浓度 μM），最终体积为0.2 100毫升 mM磷酸钾缓冲液，pH 7.4（含120 mM KCl，1 mM EDTA和5 mM DTT）通过加入2引发（时间0） μL人重组HMG-CoA还原酶的催化结构域，并在37°C的Eppendorf BioSpectrometer（配备恒温控制的细胞支架）中在1 μL等分试样的药物溶解在二甲基亚砜中。每20次监测NADPH的消耗率 秒，最多15秒 min通过扫描分光光度法[7]。

细胞增殖测定基本上如前所述进行。简言之，将来自5名不同患者的SV-SMC以全生长培养基中每孔1×104个细胞的密度接种到24孔细胞培养板中。将细胞孵育过夜，然后在无血清培养基中静置3天，然后转移到含有5种不同浓度他汀类药物的全生长培养基（10%FCS）中。所有他汀类药物都在每个患者的细胞上进行了测试。2天后更换培养基和药物，4天后使用台盼蓝和血细胞仪在一式三个孔中测定活细胞数。细胞数的增加是通过从最终细胞数（第4天）中减去起始细胞数（0天）来计算的。然后将数据标准化为对照值（无他汀类药物），以校正来自不同患者的细胞之间增殖率的差异[2]。

Animal/Disease Models: 40 8weeks old ApoE−/− mice, angiotensin II (Ang II) induced [5]
Doses: 20 mg/kg, 30 mg/kg
Route of Administration: po (oral gavage); one time/day; continuous 28-day
Experimental Results: Endoplasmic reticulum stress signaling proteins, the number of apoptotic cells, and the activation of Caspase12 and Bax were Dramatically diminished in Ang II-induced ApoE−/− mice. Pro-inflammatory cytokines such as IL-6, IL-8, and IL-1β were Dramatically inhibited.

[1]. Santodomingo-Garzón T, et al. Atorvastatin inhibits inflammatory hypernociception. Br J Pharmacol. 2006 Sep;149(1):14-22.
[2]. Turner NA, et al. Comparison of the efficacies of five different statins on inhibition of human saphenous vein smooth muscle cell proliferation and invasion. J Cardiovasc Pharmacol. 2007 Oct;50(4):458-61.
[3]. Nawrocki, J.W., et al., Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Arterioscler Thromb Vasc Biol, 1995. 15(5): p. 678-82.
[4]. Song XJ, et al. Atorvastatin inhibits myocardial cell apoptosis in a rat model with post-myocardial infarction heart failure by downregulating ER stress response. Int J Med Sci. 2011;8(7):564-72.
[5]. Li Y, et al. Inhibition of endoplasmic reticulum stress signaling pathway: A new mechanism of statins to suppress the development of abdominal aortic aneurysm. PLoS One. 2017 Apr 3;12(4):e0174821.
[6]. Ming-Bai Hu, et al. Atorvastatin induces autophagy in MDA-MB-231 breast cancer cells. Ultrastruct Pathol. Sep-Oct 2018;42(5):409-415.
[7]. In Vitro Screening for β-Hydroxy-β-methylglutaryl-CoA Reductase Inhibitory and Antioxidant Activity of Sequentially Extracted Fractions of Ficus palmata Forsk. Biomed Res Int. 2014; 2014: 762620.

C33H35FN2O5

558.65

558.253

C, 70.95; H, 6.32; F, 3.40; N, 5.01; O, 14.32

134523-00-5

Atorvastatin hemicalcium salt;134523-03-8;(3S,5S)-Atorvastatin;501121-34-2;Atorvastatin-d5 hemicalcium;222412-82-0;(rel)-Atorvastatin;110862-48-1;Atorvastatin hemicalcium trihydrate;344920-08-7;Atorvastatin-d5 sodium;222412-87-5

White to light yellow solid powder

5

112A^2

O=C(O)C[C@H](O)C[C@H](O)CCN1C(C2=CC=C(F)C=C2)=C(C3=CC=CC=C3)C(C(NC4=CC=CC=C4)=O)=C1C(C)C

XUKUURHRXDUEBC-KAYWLYCHSA-N

InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1

(3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoic acid

CI-981 CI981 Atorvastatin liptonorm Lipilou Tozalip Torvast Cardyl

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~50 mg/mL (~89.50 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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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。