雷公藤甲素对小鼠血睾屏障的损伤作用及机制OA
The damaging effect and mechanism of triptolide on the blood-testis barrier in mice
目的:探讨雷公藤甲素对小鼠血睾屏障的损伤效应及分子机制.方法:选用20～25 g健康雄性C57BL/6小鼠9只,随机分为对照组、雷公藤甲素低剂量给药组(0.2 mg/kg)和高剂量给药组(0.5 mg/kg),每组3只.持续给药28 d后,观察不同剂量雷公藤甲素干预后小鼠体重、睾丸体积及组织形态学改变,比较三组小鼠睾体比、生殖细胞凋亡水平、血睾屏障相关蛋白表达量及血睾屏障渗漏程度.结果:与对照组相比,雷公藤甲素给药组小鼠体重涨幅显著降低,睾丸重量、睾体比显著下降(P均＜0.01);HE染色显示雷公藤甲素给药组小鼠曲细精管管腔生殖细胞丢失,管腔结构出现空泡化;附睾精子数量减少,高剂量给药物组小鼠附睾精子数量进一步降低,可见大量坏死生殖细胞;TUNEL结果显示雷公藤甲素给药组小鼠曲细精管内细胞凋亡显著增加(P均＜0.01);蛋白质印迹实验显示雷公藤甲素给药组小鼠血睾屏障相关蛋白(上皮钙黏蛋白、闭合蛋白、β-连环蛋白、血管内皮钙黏蛋白、肌动蛋白相关蛋白3、紧密连接蛋白11)表达均显著下调(P均＜0.01);生物素示踪染色显示雷公藤甲素给药组小鼠睾丸的血睾屏障随给药浓度升高,屏障渗漏损伤程度逐步加剧.结论:雷公藤甲素给药可构建不同程度的小鼠血睾屏障损伤模型,其作用机制与诱导支持细胞凋亡、下调血睾屏障相关蛋白、激活氧化应激多条通路协同调控密切相关.
Objective:To investigate the damaging effects of triptolide on the blood-testis barrier and its underlying molecular mechanisms.Methods:Nine healthy male C57BL/6 mice(20-25 g)were randomly divided into control group,low-dose triptolide group(0.2 mg/kg),and high-dose triptolide group(0.5 mg/kg),with 3 animals per group.After continuous administration for 28 days,body weight,testicular volume,and testicular histomorphology were observed in mice exposed to different doses of triptolide.Intergroup comparisons of testis-to-body weight ratio,germ cell apoptosis level,expression of blood-testis barrier-related proteins and barrier leakage were performed among the three groups.Results:Compared with the control group,mice in triptolide-treated groups exhibited markedly reduced body weight gain,testicular weight and testis-to-body weight ratio(all P＜0.01).HE staining revealed massive loss of germ cells and prominent vacuolization in the seminiferous tubular lumen of triptolide-exposed mice.The sperm count in epididymal tissues was decreased upon triptolide administration,and this reduction was further aggravated in the high-dose group,accompanied by abundant necrotic germ cells.TUNEL assay revealed markedly elevated apoptosis in seminiferous tubules of triptolide-treated mice(all P＜0.01).Western blotting indicated that the expression levels of blood-testis barrier-related proteins(E-cadherin,occludin,β-catenin,VE-cadherin,Arp3,and Claudin 11)were significantly downregulated in triptolide-treated groups(all P＜0.01).Biotin tracer staining demonstrated varying degrees of blood-testis barrier injury in triptolide-treated mice,and the severity of barrier leakage increased in a dose-dependent manner.Conclusion:Triptolide treatment can be used to stably establish a mouse model of blood-testis barrier injury.Its mechanism is closely related to the synergistic regulation of multiple pathways,including Sertoli cell apoptosis,downregulated expression of blood-testis barrier-related proteins and oxidative stress response.
王宏亮;王铸;张建文;赖裕林;邓琼
深圳市龙华区人民医院泌尿外科,广东 深圳 518109深圳市龙华区人民医院泌尿外科,广东 深圳 518109深圳市龙华区人民医院泌尿外科,广东 深圳 518109深圳市龙华区人民医院泌尿外科,广东 深圳 518109深圳市龙华区人民医院泌尿外科,广东 深圳 518109
医药卫生
血睾屏障雷公藤甲素生物素细胞凋亡
blood-testis barriertriptolidebiotinapoptosis
《江苏大学学报（医学版）》 2026 (4)
305-310,6
深圳市基础研究专项/自然科学基金资助项目(JCYJ20240813114409013)深圳市龙华区医学会医学科研专项课题(2023LHMA08)
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