葛根素对双酚S致睾酮合成损伤的保护作用

阚 雅琪, 吴 梓瑶, 覃 美琳, 周 靖刚, 潘 梦芬, 曾怀 才*
桂林医学院公共卫生学院广西环境暴露组学与全生命周期健康重点实验室

摘要


目的:研究双酚 S(BPS)对睾丸间质细胞睾酮合成的抑制作用与机制及葛根素(PUE)的干预作用。
方法:用 25、50、100 mg/L BPS处理小鼠睾丸间质细胞(TM3)48 h并用 30 mg/L PUE进行干预,ELISA法检测睾
酮水平,试剂盒检测检测氧化应激指标 CAT、GSH、SOD、MDA和ROS的水平,Western blot检测细胞中 StAR和
MAPK信号通路相关蛋白表达水平。结果:BPS处理 48 h后,TM3细胞活性降低且呈剂量依赖性,同时睾酮水平降
低,经 PUE干预后睾酮水平增加。BPS引起细胞中 SOD、CAT和 GSH的活力降低,而ROS和MDA水平增加,而
PUE干预后抗氧化剂的活力增加,ROS和MDA水平降低。BPS暴露引起 StAR蛋白表达水平降低(P< 0.05),经过
PUE处理后 StAR水平增加。BPS处理后 p38/JNK MAPK信号通路上相关蛋白表达水平升高,磷酸化水平升高,PUE
干预后MAPK信号通路磷酸化水平降低。结论:BPS诱导TM3细胞发生氧化应激,激活 p38/JNK MAPK信号通路,
抑制睾酮合成,是BPS诱导雄性毒性的一种可能机制。PUE能减轻BPS引起的TM3细胞毒性作用。

关键词


双酚 S;睾酮;p38/JNK MAPK信号通路;氧化应激

全文:

PDF


参考


[1]SKLEDAR D G S J, FIC A, KLOPČIČ I,

TRONTELJ J, DOLENC MS, FINEL M, MAŠIČ LP.

Influence of metabolism on endocrine activities of bisphenol S

[J]. Chemosphere, 2016, 157: 152-9.

[2]WANG Y X, DAI W, LI Y Z, et al. Bisphenol S

induces oxidative stress-mediated impairment of testosterone

synthesis by inhibiting the Nrf2/HO-1 signaling pathway [J].

J Biochem Mol Toxicol, 2023, 37(3): e23273.

[3]PLOTNIKOV A, ZEHORAI E, PROCACCIA S,

et al. The MAPK cascades: signaling components, nuclear

roles and mechanisms of nuclear translocation [J]. Biochim

图4 BPS处理与PUE干预对TM3细胞p38/JNK MAPK信号通路的影响

(A和B)TM3细胞中 p38 MAPK细胞通路的蛋白表达水平;(C和D)TM3细胞中 JNK MAPK信号通路的蛋白

表达水平。*:P<0.05,**:P<0.01。(n=3)

44

Biophys Acta, 2011, 1813(9): 1619-33.

[4]LUO D, HE Z, YU C, et al. Role of p38 MAPK

Signalling in Testis Development and Male Fertility [J]. Oxid

Med Cell Longev, 2022, 2022: 6891897.

[5]朱清玉,郭乐薇,刘红羽,等.睾丸间质细胞睾

酮合成机制的研究进展 [J].中国畜牧杂志,2021,57(05):

28-33.

[6]HAN Y H, PARK W H. The effects of MAPK

inhibitors on antimycin A-treated Calu-6 lung cancer

cells in relation to cell growth, reactive oxygen species, and

glutathione [J]. Mol Cell Biochem, 2010, 333(1-2): 211-9.

[7]WEI S Y, CHEN Y, XU X Y. Progress on the

pharmacological research of puerarin: a review [J]. Chin J Nat

Med, 2014, 12(6): 407-14.

[8]其力根,额尔登其木格,武飞,等.葛根素缓解

己烯雌酚诱导的雄性小鼠生殖损伤研究 [J].黑龙江畜牧兽

医,2013,(21):148-50.

[9]ZHANG W, HUANG T, SUN Z, et al. Bisphenol S

exposure induces cytotoxicity in mouse Leydig cells [J]. Food

Chem Toxicol, 2022, 160: 112805.

[10]LI H T, ZHONG K, XIA Y F, et al. Puerarin

improves busulfan-induced disruption of spermatogenesis by

inhibiting MAPK pathways [J]. Biomed Pharmacother, 2023,

165: 115231.

[11]LI Y, XU L, HAO C, et al. ARTS is essential for

di-2-ethylhexyl phthalate (DEHP)-induced apoptosis of

mouse Leydig cells [J]. Ecotoxicol Environ Saf, 2024, 270:

115882.

[12]SHEN H, CAI Y, ZHU K, et al. Enniatin B1

induces damage to Leydig cells via inhibition of the Nrf2/

HO-1 and JAK/STAT3 signaling pathways [J]. Ecotoxicol

Environ Saf, 2024, 273: 116116.

[13]KARIMI S, JALILI C, MANSOURI K, et al. Effect

of melatonin on steroidogenesis-related enzymes expression

and testosterone synthesis following CoCl(2)-induced

hypoxia in TM3 Leydig cells [J]. Iran J Basic Med Sci, 2023,

26(9): 1041-6.

[14]AGARWAL A, GUPTA S, SHARMA R K. Role

of oxidative stress in female reproduction [J]. Reprod Biol

Endocrinol, 2005, 3: 28.

[15]LI X L, LIU Y L, LIU J Y, et al. 1-Nitropyrene

disrupts testicular steroidogenesis via oxidative stress-evoked

PERK-eIF2α pathway [J]. Ecotoxicol Environ Saf, 2023,

259: 115027.

[16]SHI Y, BAI J, DANG Y, et al. Protection of

apigenin against acrylonitrile-induced sperm and testis injury

in rats: involvement of activation of ASK1-JNK/p38 signaling

pathway [J]. Toxicology Research, 2021, 10(2): 159-68.

[17]LEE W-Y, PARK H-J. T-2 mycotoxin Induces

male germ cell apoptosis by ROS-mediated JNK/p38 MAPK

pathway [J]. Ecotoxicology and Environmental Safety, 2023,

262.

[18]ZHU L, YI X, ZHAO J, et al. Betulinic acid

attenuates dexamethasone-induced oxidative damage through

the JNK-P38 MAPK signaling pathway in mice [J]. Biomed

Pharmacother, 2018, 103: 499-508.

[19]QIGEN X, HAIMING C, KAI X, et al. Prenatal

DEHP Exposure Induces Premature Testicular Aging by

Promoting Leydig Cell Senescence through the MAPK

Signaling Pathways [J]. Adv Biol (Weinh), 2023, 7(10):

e2300130.

[20]HAN A, ZOU L, GAN X, et al. ROS generation

and MAPKs activation contribute to the Ni-induced

testosterone synthesis disturbance in rat Leydig cells [J].

Toxicology Letters, 2018, 290: 36-45.

[21]IJAZ M U, YAQOOB S, HAMZA A, et al.

Apigetrin ameliorates doxorubicin prompted testicular

damage: biochemical, spermatological and histological based

study [J]. Sci Rep, 2024, 14(1): 9049.

[22]常雪蕊,郭勇,齐晓龙,等.睾丸间质细胞线粒

体调控睾酮合成的研究进展 [J].中国畜牧兽医,2022,49

(01):265-72.

[23]LYU C, YUAN B, MENG Y, et al. Puerarin

Alleviates H2O2-Induced Oxidative Stress and Blood–Milk

Barrier Impairment in Dairy Cows [J]. International Journal of

Molecular Sciences, 2023, 24(9)


Refbacks

  • 当前没有refback。