石榴提取物（POMx）可降低辛伐他汀治疗的高胆固醇血症患者血清和人单核细胞源性巨噬细胞（HMDM）的动脉粥样硬化性：一项双盲、安慰剂对照、随机、前瞻性初步研究。
Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study.
机构信息
Internal Medicine E Department, Rambam Health Care Campus, Haifa, Israel.
Internal Medicine E Department, Rambam Health Care Campus, Haifa, Israel; The Lipid Research Laboratory, Rambam Health Care Campus, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
出版信息
Atherosclerosis. 2014 Jan;232(1):204-10. doi: 10.1016/j.atherosclerosis.2013.11.037. Epub 2013 Nov 19.
OBJECTIVE
To analyze pomegranate extract (POMx) effects on serum and on human HMDM atherogenicity in simvastatin - treated hypercholesterolemic patients.
METHODS AND RESULTS
Patients were randomly assigned to receive either simvastatin (20 mg/day) + vegan placebo pill (n = 11), or simvastatin (20 mg/day) + POMx pill (1g/day, n = 12). Fasting blood samples were collected at baseline and after 1 and 2 months of therapy. HMDM were collected from 3 patients in each group at baseline and after 2 months of therapy, as well as from 3 healthy subjects. After 2 months of therapy, serum LDL-cholesterol levels significantly decreased, by 23%, in the simvastatin + placebo group, and by 26% in the simvastatin + POMx group. Simvastatin + POMx therapy increased serum thiols concentration by 6%. Patients' HMDM reactive oxygen species (ROS) levels were significantly increased, by 69%, vs. healthy subjects HMDM. After 2 months of therapy, HMDM ROS levels decreased by 18% in the simvastatin + placebo group, whereas in the simvastatin + POMx group it decreased by up to 30%. A novel finding was the triglycerides levels in the patients' HMDM at baseline which were significantly higher, by 71%, vs. healthy subjects HMDM. The simvastatin + POMx, but not the simvastatin + placebo therapy, significantly reduced macrophage triglycerides content by 48%, vs. baseline levels. In addition, whereas the simvastatin + placebo therapy significantly decreased the patients' HMDM cholesterol biosynthesis rate by 33%, the simvastatin + POMx therapy further decreased it, by 44%.
CONCLUSION
The addition of POMx to simvastatin therapy in hypercholesterolemic patients improved oxidative stress and lipid status in the patient's serum and in their HMDM. These anti-atherogenic effects could reduce the risk for atherosclerosis development.
目的
分析石榴提取物（POMx）对辛伐他汀治疗高胆固醇血症患者血清和人源性单核巨噬细胞（HMDM）致动脉粥样硬化性的影响。
方法和结果
患者被随机分配接受辛伐他汀（20mg/天）+纯素安慰剂片（n=11）或辛伐他汀（20mg/天）+POMx 片（1g/天，n=12）治疗。在基线和治疗 1 个月及 2 个月时采集空腹血样。在基线和治疗 2 个月时从每组的 3 名患者以及 3 名健康受试者中采集 HMDM。治疗 2 个月后，辛伐他汀+安慰剂组血清 LDL-胆固醇水平显著下降 23%，辛伐他汀+POMx 组下降 26%。辛伐他汀+POMx 治疗使血清巯基浓度增加 6%。患者的 HMDM 活性氧（ROS）水平显著升高，与健康受试者的 HMDM 相比升高了 69%。治疗 2 个月后，辛伐他汀+安慰剂组 HMDM ROS 水平下降 18%，而辛伐他汀+POMx 组下降高达 30%。一个新发现是患者的 HMDM 中基线时的甘油三酯水平显著升高，与健康受试者的 HMDM 相比升高了 71%。辛伐他汀+POMx 治疗而非辛伐他汀+安慰剂治疗可使患者的 HMDM 中巨噬细胞甘油三酯含量显著降低 48%，与基线水平相比。此外，辛伐他汀+安慰剂治疗可使患者 HMDM 胆固醇生物合成率显著降低 33%，而辛伐他汀+POMx 治疗可进一步降低 44%。
结论
在高胆固醇血症患者中，将 POMx 添加到辛伐他汀治疗中可改善患者血清和 HMDM 的氧化应激和脂质状况。这些抗动脉粥样硬化作用可降低动脉粥样硬化发展的风险。
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