Department of Physiology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Endocrinology and Metabolism Research, and Physiology Research Centers, Kerman University of Medical Sciences, Kerman, Iran.
Int Immunopharmacol. 2018 Dec;65:190-198. doi: 10.1016/j.intimp.2018.10.009. Epub 2018 Oct 11.
In postmenopausal women, the risk of diabetic cardiovascular disease drastically increases compared with that of premenopausal women. In the present study we surveyed the effects of Tamoxifen (TAM) and 17-β-estradiol (E2) on diabetic cardiovascular dysfunction. Female wistar rats were divided into six groups: sham-control, Diabetes, Ovariectomized (OVX) + Diabetes, OVX + Diabetes + Vehicle, OVX + Diabetes + E2, OVX + Diabetes + TAM. Type 2 diabetes was induced by High Fat Diet and low doses of STZ. E2 and TAM were administrated every four days for four weeks. Results show that, TAM or E2 reduces cardiac weight, atherogenic and cardiac risk indices. Mean arterial blood pressure (MABP) increased in diabetes group, while TAM and E2 prevented MABP increment. Also, fasting blood glucose was decreased by TAM and E2. Significant decrement in the level of IL-10 was observed in diabetes group and this effect was abolished by TAM and E2. Also, treatment with TAM and E2 resulted in improved inflammatory balance in favor of anti-inflammation. Although diabetes resulted in, increment of TC and LDL, TAM and E2 reduced lipids profile. Furthermore, treatment with TAM prevented the reduction of estrogen receptors (ERs) α and β protein levels, but its effect on the ERβ protein level was higher. Our results indicated that TAM protects against diabetic cardiovascular dysfunction and is a good candidate for E2 substitution.
绝经后女性患糖尿病心血管疾病的风险比绝经前女性大幅增加。在本研究中，我们调查了他莫昔芬（TAM）和 17-β-雌二醇（E2）对糖尿病心血管功能障碍的影响。雌性 wistar 大鼠分为六组：假手术对照、糖尿病、卵巢切除（OVX）+糖尿病、OVX+糖尿病+载体、OVX+糖尿病+E2、OVX+糖尿病+TAM。2 型糖尿病通过高脂肪饮食和低剂量 STZ 诱导。E2 和 TAM 每四天给药一次，共给药四周。结果表明，TAM 或 E2 可降低心脏重量、动脉粥样硬化和心脏风险指数。糖尿病组平均动脉血压（MABP）升高，而 TAM 和 E2 可防止 MABP 升高。此外，TAM 和 E2 还降低了空腹血糖。糖尿病组观察到 IL-10 水平显著降低，TAM 和 E2 可消除这种作用。此外，TAM 和 E2 的治疗导致炎症平衡改善，有利于抗炎。尽管糖尿病导致 TC 和 LDL 增加，但 TAM 和 E2 降低了血脂谱。此外，TAM 可预防雌激素受体（ERs）α和β蛋白水平降低，但对 ERβ蛋白水平的影响更高。我们的结果表明，TAM 可预防糖尿病心血管功能障碍，是 E2 替代物的良好候选物。
