PDF(Pubmed)
Abstract：
Inorganic pyrophosphate (PPi) is the endogenous inhibitor for vascular calcification (VC). The present study was to investigate the effects of adenosine disodium triphosphate (ADTP) and alendronate sodium (AL), two exogenous PPi sources, on the atheromatous calcification (AC) in Apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were randomly divided into five groups: ApoE KO group, ApoE KO + ADTP (Low) group, ApoE KO + ADTP (High) group, ApoE KO + AL (Low) group and ApoE KO + AL (High) group. The mice in ApoE KO + ADTP (Low) group and ApoE KO + ADTP (High) group were intraperitoneally injected with ADTP with dose of 0.5 and 1.0 mg/kg/day for 2 months respectively. The mice in ApoE KO + AL (Low) group and ApoE KO + AL (High) group were intraperitoneally injected with AL with dose of 0.6 and 1.2 mg/kg/day for 2 months respectively. The age matched C57 mice were used as control group. All ApoE KO and C57 mice were fed with normal chow throughout the experiment. The calcification was evaluated using von Kossa method. The contents of PPi, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ) and interleukin-10 (IL-10) as well as the activity of alkaline phosphatase (ALP) in serum were measured. The results showed that compared with C57 mice, ApoE KO mice developed severe AC accompanied with high levels of TC, TG, LDL, IL-6, TNF-α and IFN-γ in serum and with low levels of PPi and IL-10 in serum. Both ADTP and AL dose-dependently reduced the AC in ApoE KO mice compared with that of ApoE mice, without affecting the contents of lipid profiles. In addition, ADTP and AL increased the contents of PPi and IL-10 while decreased the contents of TNF-α, IL-6 and IFN-γ in serum of ApoE KO mice, having no affection on ALP activity. The results suggested that ADTP and AL reduced AC in ApoE KO mice by increasing the PPi level and regulating the inflammation.
摘要：
无机焦磷酸盐(PPi)是血管钙化(VC)的内源性抑制剂。本研究是为了研究三磷酸腺苷二钠（ADTP）和阿仑膦酸钠（AL）的影响，两种外源PPi源，载脂蛋白E敲除（ApoEKO）小鼠的动脉粥样硬化钙化（AC）。将ApoEKO小鼠随机分为5组:ApoEKO组,ApoEKO+ADTP(低)组,ApoEKO+ADTP(高)组,ApoEKO+AL(低)组和ApoEKO+AL(高)组。ApoEKO+ADTP(低)组和ApoEKO+ADTP(高)组小鼠分别腹腔注射0.5和1.0mg/kg/d的ADTP2个月。ApoEKO+AL(低)组和ApoEKO+AL(高)组小鼠分别腹腔注射0.6和1.2mg/kg/d的AL,连续2个月。以年龄匹配的C57小鼠作为对照组。在整个实验过程中，所有ApoEKO和C57小鼠均用正常食物喂养。使用vonKossa方法评估钙化。PPI的内容，甘油三酯（TG），总胆固醇(TC),高密度脂蛋白（HDL）和低密度脂蛋白（LDL），肿瘤坏死因子α(TNF-α),白细胞介素-6（IL-6），测定血清中干扰素-γ（IFN-γ）和白细胞介素-10（IL-10）以及碱性磷酸酶（ALP）的活性。结果表明,与C57小鼠相比,ApoEKO小鼠出现严重的AC，伴有高水平的TC，TG,LDL,血清中IL-6、TNF-α和IFN-γ,血清中PPi和IL-10水平较低。与ApoE小鼠相比，ApoEKO小鼠中ADTP和AL剂量依赖性地降低AC，而不影响脂质的含量。此外,ADTP和AL增加了PPi和IL-10的含量，降低了TNF-α的含量，ApoEKO小鼠血清中的IL-6和IFN-γ,对ALP活动没有影响。结果表明，ADTP和AL通过增加PPi水平和调节炎症来降低ApoEKO小鼠的AC。
