JQ1对脂多糖所致小鼠生精功能障碍的影响  

The effects of JQ1 on LPS-induced spermatogenic dysfunction in mice

作　　者：彭莉轩 唐筱涵 张和铃 周书乐 杨嘉瑄 向宇燕 徐杨 李素云 Peng Lixuan;Tang Xiaohan;Zhang Heling;Zhou Shule;Yang Jiaxuan;Xiang YuyanXu Yang;Li Suyun(Department of Embryology and Clinical Anatomy and Reproductive Medicine Application Institute,Hengyang Medical School,University of South China,Hengyang 421001,Hunan,China;Department of Physiology and Institute of Neuroscience Medical School,Hengyang Medical School,University of South China,Hengyang 421001,Hunan,China)

机构地区：[1]南华大学衡阳医学院组胚教研室和应用解剖与生殖医学研究所,湖南衡阳421001 [2]南华大学衡阳医学院生理学教研室和神经科学研究所,湖南衡阳421001

出　　处：《中国男科学杂志》2023年第5期15-21,共7页Chinese Journal of Andrology

基　　金：湖南省自然科学基金(2021JJ30593);湖南省大学生研究性学习与创新性实验(S202210555229,S202210555240,S202210555252)。

摘　　要：目的 探讨JQ1对脂多糖(LPS)所致小鼠生精功能障碍的影响及相关机制。方法 40只8周龄雄性C57BL/6J小鼠,随机分为溶媒对照组(DMSO+NS)、模型组(DMSO+LPS)和药物干预组(JQ1+LPS),每组小鼠的数量分别为n=13、n=15和n=12,单次腹腔注射LPS诱导炎症动物模型。取材后,称量睾丸、附睾尾的重量,采用精子计数法检测小鼠精子数量,伊红染色检测精子的畸形率,苏木精-伊红(HE)染色检测睾丸形态变化;TUNEL试剂盒检测睾丸生殖细胞凋亡情况;Western blot检测凋亡基因(Bax和Bcl2)的表达情况;生化试剂盒检测睾丸丙二醛(MDA)、谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)表达情况。结果 LPS导致小鼠附睾尾重量显著下降(P<0.05),精子数量显著下降(P<0.001);精子畸形率显著升高(P<0.01);睾丸形态结构破坏,生精小管萎缩,管腔直径变小,各级生精细胞排列紊乱,管腔内精子数量减少;睾丸中凋亡细胞数量显著上调(P<0.01);Bax/Bcl2的比值显著上升(P<0.01);MDA含量显著增加(P<0.01),GSH含量显著减少(P<0.05)。经JQ1干预后,小鼠附睾尾重量、精子数量、畸形率、形态结构、细胞凋亡以及氧化应激均得到改善。结论 JQ1可能通过减轻氧化应激损伤使睾丸生精细胞凋亡减少,从而改善LPS所致小鼠生精功能障碍。Objective To explore the effect of JQ1 on Lipppolysaccharide(LPS)-induced spermatogenic dysfunction in mice and its relevant mechanisms.Methods Forty 8-week-old male C57BL/6J mice were randomly divided into the vehicle group(DMSO+NS,13 mice),the model group(DMSO+LPS,15 mice)and the intervention group(JQ1+LPS,12 mice).A single intraperitoneal injection of LPS was used to induce inflammation mouse model.After the mice were executed,their testis and cauda epididymis tissue were collected and weighed.Sperm counting method was used to measue the number of sperm.EOSIN staining was used to detect malformation rate of sperm and hematoxylin-eosin(HE)staining to analyze the morphological structure changes of testis.TUNEL kit was applied to test the apoptosis of testis germ cell.Western blot was used to detect the expressions of apoptotic genes(Bax and Bcl2),and ELISA was used to analyze the levels of malondialdehyde(MDA),glutathione(GSH)and Glutathione Oxidized(GSSG)in the testis.Results LPS resulted in significant decreases in cauda epididymis weight(P<0.05)and sperm count(P<0.001),and a significant increase in sperm malformation rate(P<0.01).The morphological structure analysis of the testis showed an obvious destruction,shrinked seminiferous tubule,smaller lumen diameter,disordered spermatid arrangement at all levels and reduced sperm amount in the lumen.The number of apoptotic cells in the testis was significantly increased(P<0.01).The ratio of Bax/Bcl2(P<0.01)and the expression of MDA were significantly increased(P<0.01),while the expression of GSH was significantly decreased(P<0.05).After JQ1 intervention,the weight of cauda epididymis,sperm count,malformation rate,morphological structure,cell apoptosis and oxidative stress were all improved.Conclusion JQl may reduce the apoptosis of testis spermatogenic cell by alleviating oxidative stress to improve LPS-induced spermatogenic dysfunction in mice.

关 键 词：JQ1 脂多糖 生精功能障碍 细胞凋亡 氧化应激 

分 类 号：R339.21[医药卫生—人体生理学]