Department of Geriatric Cardiology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
J Tradit Chin Med. 2013 Jun;33(3):384-7. doi: 10.1016/s0254-6272(13)60183-1.
To study the effects of Danhong injection (DHI) on expression of the macrophage scavenger receptor 1 (MSR1) and ATP-binding cassette, sub-family A member 1 (ABCA1) genes, which encode scavenger receptor-A I (SR-AI) and ATP-binding cassette transporter 1 (ABCA1), respectively, as a potential anti-atherosclerotic mechanism.
Human U937 cells were stimulated by incubation with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 h. These stimulated, monocyte-like cells were then incubated for 24 h with 50 mg/L oxidized low-density lipoprotein (ox-LDL, to induce foam cell formation), together with a liver X receptor (LXR) agonist or with different DHI concentrations. MSR1 and ABCA1 mRNA levels were measured by fluorescence-based quantitative PCR.
Compared with control cells (which received only ox-LDL), cells treated with both ox-LDL and 10 micromol/L LXR agonist showed lower MSR1 expression (but this effect was not statistically significant, P > 0.05) and higher ABCA1 expression (P < 0.01). Cells that received ox-LDL and 3 mL/L DHI possessed higher MSR1 mRNA levels than the controls, whereas cells treated with ox-LDL and higher DHI concentrations (10, 30 or 60 mL/L) showed lower MSR1 expression levels (but the differences observed between DHI concentration groups were not statistically significant, P > 0.05). ABCA1 expression in cells treated with ox-LDL and 3, 10 or 30 mL/L DHI was higher than in the control cells, and increased with increasing DHI concentration (P < 0.05). ABCA1 expression in cells treated with ox-LDL and the highest DHI concentration tested (60 mL/L) was not significantly different from that in the controls. ABCA1 mRNA levels in cells treated with ox-LDL and DHI were similar to, or lower than, those in cells treated with ox-LDL and the LXR agonist.
DHI does not affect MSR1 mRNA levels in ox-LDL-treated U937 cells. However, at certain concentrations (10 and 30 mL/L), DHI significantly increases ABCA1 mRNA levels. Therefore, the anti-atherosclerotic action of DHI might be mediated by an increased expression of ABCA1.
研究丹红注射液(DHI)对巨噬细胞清道夫受体 1(MSR1)和三磷酸腺苷结合盒,A 族成员 1(ABCA1)基因表达的影响,这两个基因分别编码清道夫受体-A I(SR-AI)和三磷酸腺苷结合盒转运蛋白 1(ABCA1),作为一种潜在的抗动脉粥样硬化机制。
用人单核细胞 U937 细胞孵育 100 nM 佛波醇 12-肉豆蔻酸 13-醋酸酯(PMA)48 h 进行刺激。然后将这些被刺激的单核细胞样细胞与 50 mg/L 氧化低密度脂蛋白(ox-LDL,诱导泡沫细胞形成)孵育 24 h,同时加入肝 X 受体(LXR)激动剂或不同浓度的 DHI。通过荧光定量 PCR 测量 MSR1 和 ABCA1 mRNA 水平。
与仅接受 ox-LDL 的对照细胞相比,同时接受 ox-LDL 和 10 微摩尔/L LXR 激动剂的细胞 MSR1 表达水平较低(但差异无统计学意义,P>0.05),ABCA1 表达水平较高(P<0.01)。与对照相比,接受 ox-LDL 和 3 mL/L DHI 的细胞具有更高的 MSR1 mRNA 水平,而接受更高浓度 ox-LDL 和 DHI(10、30 或 60 mL/L)的细胞 MSR1 表达水平较低(但各组之间的差异无统计学意义,P>0.05)。与对照相比,用 ox-LDL 和 3、10 或 30 mL/L DHI 处理的细胞的 ABCA1 表达水平较高,且随 DHI 浓度增加而增加(P<0.05)。用 ox-LDL 和试验中最高浓度 DHI(60 mL/L)处理的细胞的 ABCA1 表达水平与对照相比无显著差异。用 ox-LDL 和 DHI 处理的细胞的 ABCA1 mRNA 水平与用 ox-LDL 和 LXR 激动剂处理的细胞相似或低于用 ox-LDL 和 LXR 激动剂处理的细胞。
DHI 不影响 ox-LDL 处理的 U937 细胞中 MSR1 mRNA 水平。然而,在某些浓度(10 和 30 mL/L)下,DHI 显著增加 ABCA1 mRNA 水平。因此,DHI 的抗动脉粥样硬化作用可能是通过 ABCA1 的表达增加介导的。