Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran.
Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Fundam Clin Pharmacol. 2023 Apr;37(2):287-295. doi: 10.1111/fcp.12839. Epub 2022 Oct 24.
Diabetes induces a disorder in mitochondrial activity, which causes damage to the nuclear and mitochondrial DNA and ultimately increases the release of inflammatory cytokines and damages the sciatic nerve and dorsal root ganglion and induces neuropathy. It has been shown that progesterone has anti-inflammatory and antioxidative effects and prevents nerve cell damage. Therefore, the aim of this experiment was to investigate the effect of progesterone receptor neuroprotection on diabetic neuropathy. Forty male Sprague-Dawley rats were divided into four groups, including control group, diabetic control group, diabetic control group + progesterone (30 mg/kg), and diabetic control group + combination of progesterone (30 mg/kg) and RU486 (10 mg/kg). After the induction of diabetes, blood glucose level, body weight, behavioral tests, electrophysiological tests, oxidative and inflammatory factors, and histological parameters were measured. Progesterone treatment significantly reduced the level of sensitivity to hot plate without significant effect on glucose level, and significant changes were also observed in the results of tail flick test. In addition, the results showed that the administration of progesterone can improve MNCV and significantly reduce the serum levels of oxidative stress and inflammatory factors, as well as inflammation and edema around the sciatic nerve. However, RU486 inverted the beneficial effects of progesterone. Progesterone can be considered as a protective agent in reducing DN because of its ability to reduce inflammation and nerve damage. In addition, RU486, a progesterone receptor blocker, inhibits the beneficial effects of progesterone on the DN; thus, progesterone receptors play an important role in the neuroprotective effect of progesterone.
糖尿病可引起线粒体活性紊乱，导致核和线粒体 DNA 损伤，最终增加炎症细胞因子的释放，损害坐骨神经和背根神经节，并引发神经病变。已证实孕激素具有抗炎和抗氧化作用，可防止神经细胞损伤。因此，本实验旨在研究孕激素受体神经保护作用对糖尿病神经病变的影响。将 40 只雄性 Sprague-Dawley 大鼠分为四组，包括对照组、糖尿病对照组、糖尿病对照组+孕激素（30mg/kg）和糖尿病对照组+孕激素（30mg/kg）+RU486（10mg/kg）。糖尿病诱导后，测量血糖水平、体重、行为测试、电生理测试、氧化和炎症因子以及组织学参数。孕激素治疗可显著降低热板敏感性，而对血糖水平无明显影响，尾巴拍打试验结果也有显著变化。此外，结果表明，孕激素的给药可改善 MNCV，并显著降低血清氧化应激和炎症因子水平，以及坐骨神经周围的炎症和水肿。然而，RU486 反转了孕激素的有益作用。由于孕激素具有减轻炎症和神经损伤的能力，因此可将其视为减少糖尿病肾病的保护剂。此外，孕激素受体阻断剂 RU486 抑制了孕激素对糖尿病肾病的有益作用；因此，孕激素受体在孕激素的神经保护作用中发挥重要作用。
