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雾化细颗粒物(PM)污染对小鼠卵巢的损害:可能的保护药物及机制

Ovarian Damages Produced by Aerosolized Fine Particulate Matter (PM) Pollution in Mice: Possible Protective Medications and Mechanisms.

作者信息

Gai Hui-Fang, An Jian-Xiong, Qian Xiao-Yan, Wei Yong-Jie, Williams John P, Gao Guo-Lan

机构信息

Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong 261000; Department of Obstetrics and Gynecology, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing 100012, China.

Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing 100012, China.

出版信息

Chin Med J (Engl). 2017 Jun 20;130(12):1400-1410. doi: 10.4103/0366-6999.207472.

Abstract

BACKGROUND

Ambient aerosol fine particulate matter (PM2.5) is associated with male reproductive toxicity in experiments and may have adverse effects in the female. However, studies evaluating the protective effects and precise mechanisms of aspirin, Vitamin C, Vitamin E, or ozone against toxic effects of PM2.5are sparse. This study was conducted to investigate the possible protective effects and mechanisms of aspirin, Vitamin C, Vitamin E, or ozone on fertility in female mice treated with PM2.5.

METHODS

Eighty-four ICR mice were divided into six groups: control group, PM2.5group, PM2.5 + aspirin group, PM2.5 + Vitamin C group, PM2.5 + Vitamin E group, and PM2.5 + ozone group. PM2.5was given by intratracheal instillation every 2 days for 3 weeks. Aspirin, Vitamin C, and Vitamin E were given once a day by oral gavage for 3 weeks, and ozone was administered by intraperitoneal injection once a day for 3 weeks. The levels of anti-Müllerian hormone (AMH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using enzyme-linked immunosorbent assay. Western blotting analysis was used to analyze the expressions of Bcl-2, Bax, and caspase-3 in ovaries. Changes in histological structure were examined by light microscope and electron microscopy was used to detect ultramicrostructure.

RESULTS

The results demonstrated that PM2.5 decreased AMH levels (P < 0.001); however, aspirin (P < 0.001), Vitamin C (P < 0.001), Vitamin E (P = 0.001), and ozone (P = 0.002) alleviated the decrease. Changes of IL-6, TNF-α, 8-OHdG, Bax/Bcl-2, and caspase-3 in PM2.5group were increased compared to control group (P < 0.001), while in PM2.5 + aspirin, PM2.5 + Vitamin C, PM2.5 + Vitamin E, and PM2.5 + ozone groups, they were statistically decreased compared to PM2.5group (P < 0.001 or P< 0.05).

CONCLUSIONS

PM2.5cause the damage of ovaries, and aspirin, Vitamin C, Vitamin E, and ozone antagonizes the damage. The protective mechanism is probably due to its ability to blunt the inflammatory and oxidative stress caused by PM2.5, which subsequently suppressing the expression of apoptotic regulatory protein and reducing the incidence of ovary apoptosis.

摘要

背景

环境气溶胶细颗粒物(PM2.5)在实验中与雄性生殖毒性有关,对雌性可能也有不良影响。然而,评估阿司匹林、维生素C、维生素E或臭氧对PM2.5毒性作用的保护作用及精确机制的研究较少。本研究旨在探讨阿司匹林、维生素C、维生素E或臭氧对接受PM2.5处理的雌性小鼠生育能力的可能保护作用及机制。

方法

84只ICR小鼠分为6组:对照组、PM2.5组、PM2.5 + 阿司匹林组、PM2.5 + 维生素C组、PM2.5 + 维生素E组和PM2.5 + 臭氧组。每2天经气管内滴注PM2.5,持续3周。阿司匹林、维生素C和维生素E每天经口灌胃给药1次,持续3周,臭氧每天腹腔注射给药1次,持续3周。采用酶联免疫吸附测定法检测抗苗勒管激素(AMH)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和8-羟基-2'-脱氧鸟苷(8-OHdG)的水平。采用蛋白质免疫印迹分析卵巢中Bcl-2、Bax和半胱天冬酶-3的表达。通过光学显微镜检查组织结构变化,并用电子显微镜检测超微结构。

结果

结果表明,PM2.5降低了AMH水平(P < 0.001);然而,阿司匹林(P < 0.001)、维生素C(P < 0.001)、维生素E(P = 0.001)和臭氧(P = 0.002)减轻了这种降低。与对照组相比,PM2.5组中IL-6、TNF-α、8-OHdG、Bax/Bcl-2和半胱天冬酶-3的变化增加(P < 0.001),而在PM2.5 + 阿司匹林组、PM2.5 + 维生素C组、PM2.5 + 维生素E组和PM2.5 + 臭氧组中,与PM2.5组相比,它们在统计学上有所降低(P < 0.001或P < 0.05)。

结论

PM2.5会导致卵巢损伤,而阿司匹林、维生素C、维生素E和臭氧可拮抗这种损伤。其保护机制可能是由于其能够减轻PM2.5引起的炎症和氧化应激,进而抑制凋亡调节蛋白的表达并降低卵巢细胞凋亡的发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9d/5463468/f9c7523bd842/CMJ-130-1400-g001.jpg

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