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维生素D3给药及高脂饮食对实验性诱导的多囊卵巢综合征中氧化应激和炎症的影响。

The impact of vitamin D3 administration and of high fat diet on oxidative stress and inflammation in experimentally induced polycystic ovary syndrome.

作者信息

Vulcan Talida, Suciu Tudor Sergiu, Lenghel Lavinia Manuela, Toma Vlad Alexandru, Decea Nicoleta, Moldovan Remus, Mitrea Daniela-Rodica, Baldea Ioana, Filip Gabriela Adriana

机构信息

Department of Dermatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Department of Maxillofacial Surgery and Radiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

出版信息

Med Pharm Rep. 2024 Oct;97(4):516-527. doi: 10.15386/mpr-2798. Epub 2024 Oct 30.

Abstract

BACKGROUND

Polycystic ovary syndrome (PCOS) is commonly associated with obesity and may be exacerbated by the lack of vitamin D3.

AIM

The study aimed to investigate the effects of vitamin D3 administration in female rats with PCOS and prolonged high fat diet (HFD).

METHODS

Forty-four female Wistar rats, 180-200 g, 10 weeks old, were randomly allocated into 2 groups (n=22) that received a single dose intramuscular injection of: sesame oil (group I), or estradiol valerate (5 mg) in sesame oil (group II). After 4 weeks, intraovarian cysts developed in group II, as evidenced by ultrasonography. In the next step, half of rats from each group received standard diet (SD) and the other half high fat diet, through oral gavage, for 17 weeks, the following groups being obtained: Control (SD), HFD, PCOS (PCOS+SD) and PCOS+HFD. Next, all the rats received, for 5 weeks, 500 UI/kg/day vitamin D3, through oral gavage. Lipid peroxidation was assessed through malondialdehyde level in the ovary and periovarian tissue and the inflammation was quantified in ovary by NFkB, pNFkB, NRF2 and SOD1 expressions. Ovaries from all groups were collected for histopathological analysis. Blood samples were taken to evaluate the basal insulin, triglycerides and total cholesterol levels throughout the experiment.

RESULTS

Both groups with PCOS recorded significant increases of malondialdehyde in ovaries (p<0.001) and in periovarian tissue, especially in PCOS+HFD (p<0.05), even after vitamin D3 administration. PCOS+HFD group treated with vitamin D3 showed a high degree of inflammation in ovarian histopathology but with decreased pNFkB expression (p<0.01) while PCOS group recorded an increased SOD1 expression (p<0.05). Additionally, vitamin D3 treatment attenuated the insulin level (p<0.001) in PCOS and in HFD groups and the total cholesterol level in PCOS+HFD group, but triglycerides recordings were without statistical significance (p>0.05). HFD induced inflammation in ovaries, evidenced histologically and through increases of COX2 expressions (p<0.05) without significant influences on oxidative stress and on cholesterol levels.

CONCLUSIONS

Polycystic ovary syndrome is associated with oxidative stress and inflammation in the ovary tissue and in blood with increased levels of insulin, total cholesterol and triglycerides that might be partially mitigated by vitamin D3 oral administration.

摘要

背景

多囊卵巢综合征(PCOS)通常与肥胖相关,且可能因维生素D3缺乏而加重。

目的

本研究旨在探讨给予维生素D3对患有PCOS并长期高脂饮食(HFD)的雌性大鼠的影响。

方法

将44只10周龄、体重180 - 200 g的雌性Wistar大鼠随机分为2组(n = 22),分别接受单次肌肉注射:芝麻油(I组),或芝麻油中戊酸雌二醇(5 mg)(II组)。4周后,超声检查显示II组出现卵巢内囊肿。下一步,每组一半大鼠经口灌胃给予标准饮食(SD),另一半给予高脂饮食,持续17周,从而得到以下几组:对照组(SD)、HFD组、PCOS组(PCOS + SD)和PCOS + HFD组。接下来,所有大鼠经口灌胃给予500 UI/kg/天的维生素D3,持续5周。通过检测卵巢和卵巢周围组织中的丙二醛水平评估脂质过氧化,并通过NFkB、pNFkB、NRF2和SOD1的表达对卵巢炎症进行定量分析。收集所有组的卵巢进行组织病理学分析。在整个实验过程中采集血样以评估基础胰岛素、甘油三酯和总胆固醇水平。

结果

两组PCOS大鼠卵巢(p < 0.001)和卵巢周围组织中的丙二醛均显著增加,尤其是PCOS + HFD组(p < 0.05),即使在给予维生素D3后也是如此。维生素D3治疗的PCOS + HFD组在卵巢组织病理学上显示高度炎症,但pNFkB表达降低(p < 0.01),而PCOS组SOD1表达增加(p < 0.05)。此外,维生素D3治疗使PCOS组和HFD组的胰岛素水平降低(p < 0.001),并使PCOS + HFD组的总胆固醇水平降低,但甘油三酯水平无统计学意义(p > 0.05)。HFD诱导卵巢炎症,组织学检查及COX2表达增加(p < 0.05)可证实,但对氧化应激和胆固醇水平无显著影响。

结论

多囊卵巢综合征与卵巢组织及血液中的氧化应激和炎症相关,伴有胰岛素、总胆固醇和甘油三酯水平升高,口服维生素D3可能会部分缓解这些情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6476/11534383/30eb54f57490/cm-97-516f1.jpg

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