Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Steroids. 2022 Jul;183:109023. doi: 10.1016/j.steroids.2022.109023. Epub 2022 Mar 28.
The beneficial effects of the administration of selective estrogen receptor modulators (SERMs) and estrogen (E2), alone or in combination with each other, have been reported in postmenopausal diabetic cardiovascular dysfunction. In the present study, we determined the mechanism of action of SERMs and E2 on inflammatory balance, angiotensin II (Ang II) serum levels, and glycemic profile in a postmenopausal diabetic rat model.
Ovariectomized rats with type 2 diabetes received daily SERMs (tamoxifen and raloxifene) and E2 for one month. After treatment, cardiovascular risk indices, glycemic profile, and serum Ang II, TNF-α and IL-10 levels were measured.
Type 2 diabetes caused an abnormal glycemic profile, which was exacerbated by ovariectomy. All treatments inhibited the effects of diabetes and ovariectomy on the glycemic profile, with combined treatments (SERMs + E2) showing stronger effects. Cardiovascular risk indices that became abnormal by diabetes and worsened by ovariectomy were improved in all treatment modalities. Also, combined treatment reduced serum Ang II, TNF-α, and the ratio of TNF-α to IL-10, indicating an improvement in inflammatory balance.
Our study showed the administration of SERMs and E2, alone or in combination, could be an effective alternative in the treatment of menopausal diabetes, and generally, the beneficial effects of combined treatments were more effective than the effects of E2 or SERMs alone. It appears that E2 or SERMs benefit the cardiovascular system by improving inflammatory balance and reducing Ang II levels.
已有研究报道，选择性雌激素受体调节剂（SERMs）和雌激素（E2）单独或联合使用对绝经后糖尿病心血管功能障碍具有有益作用。在本研究中，我们确定了 SERMs 和 E2 对绝经后糖尿病大鼠模型中炎症平衡、血管紧张素 II（Ang II）血清水平和血糖谱的作用机制。
2 型糖尿病去卵巢大鼠每天接受 SERMs（他莫昔芬和雷洛昔芬）和 E2 治疗一个月。治疗后，测量心血管风险指数、血糖谱以及血清 Ang II、TNF-α 和 IL-10 水平。
2 型糖尿病导致血糖谱异常，而去卵巢加重了这种异常。所有治疗均抑制了糖尿病和去卵巢对血糖谱的影响，联合治疗（SERMs+E2）的效果更强。糖尿病和去卵巢导致的心血管风险指数异常得到改善。此外，联合治疗降低了血清 Ang II、TNF-α 和 TNF-α 与 IL-10 的比值，表明炎症平衡得到改善。
本研究表明，单独或联合使用 SERMs 和 E2 可作为治疗绝经后糖尿病的有效方法，联合治疗的有益效果通常比单独使用 E2 或 SERMs 更有效。似乎 E2 或 SERMs 通过改善炎症平衡和降低 Ang II 水平有益于心血管系统。
