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水飞蓟素减轻甘油三酯诱导的心脏脂肪毒性。

Triglyceride-induced cardiac lipotoxicity is mitigated by Silybum marianum.

机构信息

Cardiovascular Program-ICCC, Research Institute Hospital de La Santa Creu I Sant Pau, IIB-Sant Pau, Barcelona, Spain; CiberCV, Institute Carlos III, Madrid, Spain.

Cardiovascular Program-ICCC, Research Institute Hospital de La Santa Creu I Sant Pau, IIB-Sant Pau, Barcelona, Spain.

出版信息

Atherosclerosis. 2021 May;324:91-101. doi: 10.1016/j.atherosclerosis.2021.03.014. Epub 2021 Mar 27.

DOI:10.1016/j.atherosclerosis.2021.03.014
PMID:33857761
Abstract

BACKGROUND AND AIMS

Silybum marianum (SM) is an herbal product with cytoprotective and antioxidant properties. We have previously demonstrated that SM ameliorates ventricular remodeling and improves cardiac performance. Here, we evaluated whether SM could exert beneficial effects against cardiac lipotoxicity in a pig model of closed-chest myocardial infarction (MI).

METHODS

Study 1 investigated the effect of SM administration on lipid profile and any potential SM-related adverse effects. Animals received SM or placebo during 10 days and were afterward sacrificed. Study 2 evaluated the effectiveness of SM daily administration in reducing cardiac lipotoxicity in animals subjected to a 1.5h myocardial infarction (MI), who were subsequently reperfused for 2.5h and euthanized or kept under study for three weeks and then sacrificed.

RESULTS

Animals administered a 10-day SM regime presented a sharp decline in plasma triglyceride levels vs. controls, with no other modifications in lipid profile. The decrease in triglyceride concentration was accompanied by a marked reduction in triglyceride intestinal absorption and glycoprotein-P expression. Three weeks post-MI the triglyceride content in the ischemic myocardium of the SM-treated animals was significantly lower than in the ischemic myocardium of placebo-controls. This effect was associated with an enhanced cardiac expression of PPARγ and triglyceride clearance receptors. This long-term SM-administration induced a lower expression of lipid receptors in subcutaneous adipose tissue. No SM-related side-effects were registered.

CONCLUSION

SM administration reduces plasma triglyceride levels through attenuation of triglyceride intestinal absorption and modulates cardiac lipotoxicity in the ischemic myocardium, likely contributing to improve ventricular remodeling.

摘要

背景与目的

水飞蓟(SM)是一种具有细胞保护和抗氧化特性的草药产品。我们之前已经证明,SM 可以改善心室重构并改善心脏功能。在这里,我们评估了 SM 是否可以在闭胸心肌梗死(MI)猪模型中对心脏脂肪毒性发挥有益作用。

方法

研究 1 调查了 SM 给药对脂质谱的影响以及任何潜在的 SM 相关不良反应。动物在 10 天内接受 SM 或安慰剂治疗,然后处死。研究 2 评估了 SM 每日给药在减少接受 1.5 小时心肌梗死(MI)后动物心脏脂肪毒性的有效性,这些动物随后再灌注 2.5 小时并安乐死,或在研究中保留三周,然后处死。

结果

接受 10 天 SM 治疗方案的动物与对照组相比,血浆甘油三酯水平急剧下降,脂质谱无其他变化。甘油三酯浓度的降低伴随着甘油三酯肠道吸收和糖蛋白-P 表达的明显减少。MI 后 3 周,SM 治疗动物缺血心肌中的甘油三酯含量明显低于安慰剂对照动物的缺血心肌。这种作用与心脏中 PPARγ 和甘油三酯清除受体的表达增强有关。这种长期 SM 给药导致皮下脂肪组织中脂质受体的表达降低。未记录到与 SM 相关的副作用。

结论

SM 给药通过减少甘油三酯的肠道吸收来降低血浆甘油三酯水平,并调节缺血心肌中的心脏脂肪毒性,可能有助于改善心室重构。

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