ISRIB对脂多糖所致小鼠生精功能障碍的影响  

The effect of ISRIB on LPS-induced spermatogenic dysfunction in mice

作　　者：赵密 彭莉轩 谭钰融 刘铭柔 徐杨 周华茂 向宇燕 李素云 ZHAO Mi;PENG Lixuan;TAN Yurong;LIU Mingrou;XU Yang;ZHOU Huamao;XIANG Yuyan;LI Suyun(Nanhua Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421002,Hunan,China;Institute of Applied Anatomy and Reproductive Medicine,University of South China,Hengyang 421001,Hunan,China;Physiology Teaching and Research Office,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附属南华医院,湖南衡阳421002 [2]南华大学衡阳医学院应用解剖与生殖医学研究所,湖南衡阳421001 [3]南华大学衡阳医学院生理学教研室,湖南衡阳421001

出　　处：《中南医学科学杂志》2024年第3期333-337,共5页Medical Science Journal of Central South China

基　　金：湖南省自然科学基金项目(2023JJ60358,2021JJ30593);湖南省教育厅重点项目(21A0287);南华大学大学生研究性学习与创新性实验资助项目(X202310555116,X202310555130)。

摘　　要：目的探讨ISRIB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27只ICR小鼠随机均分为对照组、模型组和模型+ISRIB组。单次腹腔注射LPS诱导生精功能障碍小鼠模型。比较各组睾丸、附睾尾质量、精子数量和精子畸形率。HE染色检测睾丸形态结构;Real-time PCR检测炎症因子[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)]水平;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)水平。结果LPS导致模型组小鼠精子数量减少,精子畸形率升高(P<0.001);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;炎症因子IL-1β、IL-6和TNF-α升高(P<0.05,P<0.0001);GSH减少,MDA和GSSG增加(P<0.01),GSH/GSSG下降(P<0.001)。经ISRIB干预后,模型+ISRIB组小鼠精子数量、畸形率和睾丸形态结构均得到改善,炎症因子和氧化应激得到部分改善(P<0.05)。结论ISRIB可能通过减轻氧化应激使睾丸炎症减少,从而改善LPS所致小鼠生精功能障碍。Aim To explore the effect of ISRIB on lipopolysaccharide(LPS)-induced spermatogenic dysfunction in mice and its relevant mechanism.Methods 27 ICR mice were randomly divided into a control group,a model group,and a model+ISRIB group.A single intraperitoneal injection of LPS was used to establish the spermatogenic dysfunction mice model.The mass,sperm count,and sperm deformity rate of testicles and epididymal tail in each group were compared.HE staining was used to detect testicular morphology and structure.Real-time PCR was used to detect the level of inflammatory factors interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α.The biochemical reagent kits were used to detect the levels of malondialdehyde(MDA),glutathione(GSH),and oxidized glutathione(GSSG)in the testes.Results In model mice,LPS caused a decrease in sperm count and an increase in sperm deformity rate(P<0.001),the morphology and structure of the testes were disrupted,the seminiferous tubules shrink,the diameter of the lumen became smaller,the arrangement of spermatogenic cells at all levels was disordered,and the number of sperm in the lumen was decreased,inflammatory factor IL-1,IL-6 and TNF-αwere elevated(P<0.05,P<0.0001);GSH was decreased,MDA and GSSG increased(P<0.01),and GSH/GSSG decreased(P<0.001).After ISRIB intervention,the number of sperm,deformity rate,and testis morphological structure of model+ISRIB group mice were improved,and there was a trend of improvement in inflammatory factors and oxidative stress(P<0.05).Conclusion ISRIB alleviated LPS-induced spermatogenic dysfunction in mice,which may be partially due to the decrease of oxidative stress level in testis.

关 键 词：ISRIB 脂多糖 生精功能障碍 炎症因子 氧化应激 

分 类 号：R339[医药卫生—人体生理学]