【妇产科.2019】N-乙酰半胱氨酸和α-硫辛酸通过雌激素非依赖性机制改善抗氧化防御，并降低卵巢切除大鼠的氧化应激、炎症和血脂水平

文献DOI：10.1016/j.jnutbio.2019.02.012

文献PMID：30951973

文献原文链接：http://doi.org.sci-hub.tw/10.1016/j.jnutbio.2019.02.012

N-乙酰半胱氨酸和α-硫辛酸通过雌激素非依赖性机制改善抗氧化防御，并降低卵巢切除大鼠的氧化应激、炎症和血脂水平

Abstract

Sexual hormone deficiency has been associated with metabolic changes, oxidative stress and subclinical inflammation in postmenopausal women. Hormone replacement therapies are effective in many instances, even though some patients either do not respond or are not eligible. The aim of this study was to evaluate the impact of short- (15 days) versus long-term (60 days) sexual hormone depletion and whether antioxidant supplementation with N-acetylcysteine (NAC) and alpha-Lipoic Acid (LA) improves oxidative stress, metabolic, and inflammatory parameters in ovariectomized (OVX) rats. Short-term OVX rapidly depleted circulating estrogen, causing uterine atrophy and body weight gain without affecting oxidative damage, inflammatory and lipid metabolism markers. In contrast, long-term OVX augmented oxidative damage in serum and peripheral tissues as well as increased serum total cholesterol, TNF-α and IL6 levels. Triglycerides, glucose and HDL cholesterol were not altered. Long-term OVX-induced oxidative stress was associated with depletion of GSH and total nonenzymatic antioxidants as well as decreased activity of Glutathione Peroxidase (GPx) and Glutathione Reductase (GR), but not Superoxide Dismutase (SOD) and Catalase (CAT). NAC and LA supplementation prevented GSH and total non-enzymatic antioxidants depletion as well as restored GPx and GR activities, TNF-α, IL6 and cholesterol in OVX rats. NAC and LA effects appear to be independent on NRF2 activation and estrogen-like activity, since NAC/LA did not promote NRF2 activation and were not able to emulate estrogen effects in OVX rats and estrogen-receptor-positive.

摘要翻译：

性激素缺乏与绝经后妇女的代谢变化、氧化应激和亚临床炎症有关。激素替代疗法在许多情况下是有效的，即使一些患者要么没有反应或没有资格。本研究的目的是评估短期（15天）与长期（60天）性激素耗竭的影响，以及抗氧化剂补充N-乙酰半胱氨酸（NAC）和α-硫辛酸（LA）是否能改善氧化应激卵巢切除（OVX）大鼠的代谢和炎症参数。短期OVX迅速耗尽循环雌激素，导致子宫萎缩和体重增加，而不影响氧化损伤、炎症和脂质代谢标志物。相反，长期OVX增加血清和外周组织中氧化损伤以及血清总胆固醇、TNF-α和IL6水平的增加。甘油三酯、葡萄糖和HDL胆固醇没有改变。长期OVX诱导的氧化应激与GSH和总非酶抗氧化剂的消耗以及谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的活性降低相关，但不与超氧化物歧化酶（SOD）和过氧化氢酶（CAT）相关。 NAC和LA补充剂可以防止GSH和总的非酶抗氧化剂耗尽，并恢复OVX大鼠的GPx和GR活性，改善TNF-α、IL6和胆固醇。 NAC和LA效应似乎与NRF2活化和雌激素样活性无关，因为NAC / LA不促进NRF2活化，并且不能模拟OVX大鼠中的雌激素效应和雌激素受体阳性。