Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, China.
Acta Pharmacol Sin. 2010 Oct;31(10):1350-8. doi: 10.1038/aps.2010.109. Epub 2010 Sep 13.
The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/- mice) fed a "Western-style diet" and the effect of simvastatin intervention.
Male ApoE-/- mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg⁻¹·d⁻¹) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/- mice.
ApoE-/- mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05).
ApoE-/- mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.
研究载脂蛋白 E 缺陷（ApoE-/-）小鼠在“西方饮食”喂养下的心肌肥厚和纤维化情况，以及辛伐他汀干预的效果。
雄性 ApoE-/- 小鼠（n=36）从 8 周龄开始喂养“西方饮食”。16 周后，随机给予辛伐他汀（25mg·kg⁻¹·d⁻¹）或生理盐水（对照组）灌胃 8、16 或 24 周。用苏木精-伊红染色法测定左心室（LV）壁厚度和心肌细胞直径，用 Masson 染色法评估心肌基质纤维化程度。实时定量聚合酶链反应和 Western 印迹分析用于测定 ApoE-/- 小鼠心肌中基质金属蛋白酶-9（MMP-9）、组织蛋白酶 S（Cat S）和过氧化物酶体增殖物激活受体（PPARs）的 mRNA 和蛋白表达。
喂养“西方饮食”的 ApoE-/- 小鼠总胆固醇（TC）、LV 壁厚度、心肌细胞直径和 LV 胶原含量随年龄呈显著的依赖性增加（P<0.05）。与对照组相比，辛伐他汀治疗组在 40 周时 LV 壁厚度、心肌细胞直径和 LV 胶原含量明显降低（P<0.05）。此外，与对照组相比，辛伐他汀治疗还显著抑制了 MMP-9 和 Cat S 的 mRNA 和蛋白表达，并在 32 和 40 周时增加了 PPARα和 PPARγ的 mRNA 和蛋白表达（P<0.05）。
喂养“西方饮食”的 ApoE-/- 小鼠存在心肌肥厚和纤维化，且随年龄增加而加重。辛伐他汀治疗可抑制心肌肥厚和纤维化的发展，其作用机制可能是通过增加 PPARα和 PPARγ的水平和降低 TC、MMP-9 和 Cat S 的水平来实现的。
