外源性雄激素上调细胞自噬致使大鼠附睾组织损伤
首发时间:2020-08-31
摘要:目的:探讨外源性雄激素致大鼠附睾组织损伤的作用及其可能机制。方法:32只雄性SD大鼠(每组8只)随机分成4组:control组、丙酸睾丸酮 (TP) 组、TP+甘草甜素(GLY,HMGB1抑制剂)组、TP+氯喹 (CQ,自噬抑制剂) 组。干预21d后,测量各组大鼠体重、附睾湿重,计算附睾指数;HE染色观察各组大鼠附睾组织病理学变化;采用western blotting法检测附睾组织LC3B-II、P62、Beclin1、HMGB1表达变化。结果:TP组大鼠处理21d后,附睾湿重、附睾指数均明显增加(P<0.01);附睾输出小管管腔形状不规则、上皮细胞水肿、坏死脱落、基底膜不完整、精子数量减少、部分上皮和间质细胞增生、炎性细胞浸润;附睾组织LC3B-II、Beclin1、HMGB1蛋白表达均增加(P<0.05)。联合给予TP和Gly后,附睾湿重、指数均减小(P<0.05),附睾组织LC3B-II/I、Beclin-1的蛋白水平下调,附睾组织损伤改善。联合给予TP与CQ,附睾湿重减小(P<0.05),P62蛋白水平增加,附睾组织损伤改善。结论:外源性雄激素可能通过上调HMGB1介导细胞自噬致附睾组织损伤。
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Exogenous androgens up-regulate autophagy and cause damage to rat epididymis
Abstract:Objective: To investigate the effect of exogenous androgens on the damage of rat epididymis and its possible mechanism. Methods: 32 male SD rats (8 in each group) were randomly divided into 4 groups: control group, testosterone propionate (TP) group, TP+glycyrrhizin (GLY, HMGB1 inhibitor) group, TP+chloroquine (CQ, autophagy) Inhibitor) group. After 21 days of intervention, the body weight and wet weight of the epididymis were measured, and the epididymal index was calculated; HE staining was used to observe the histopathological changes of the epididymis in each group; western blotting was used to detect the expression of LC3B-II, P62, Beclin1, HMGB1 in the epididymis. Results: After 21 days of treatment in the TP group, the wet weight of the epididymis and the index of the epididymis increased significantly (P<0.01); Irregular shape of the lumen of the epididymal efferent tubule, edema of epithelial cells, necrosis and shedding, incomplete basement membrane, reduced sperm count, part of epithelial and mesenchymal cell proliferation, and inflammatory cell infiltration; The expression of LC3B-II, Beclin1, HMGB1 protein in epididymal tissue increased (P<0.05). After combined administration of TP and Gly, the wet weight and index of the epididymis decreased (P<0.05), the protein levels of LC3B-II/I and Beclin-1 in epididymis tissue were down-regulated, and the damage of epididymis tissue was improved. Combined administration of TP and CQ, the wet weight of the epididymis decreased (P<0.05), the level of P62 protein increased, and the damage of epididymal tissue was improved. Conclusion: Exogenous androgens may upregulate HMGB1 to mediate autophagy and induce epididymal tissue damage.
Keywords: Epididymis Androgen Autophagy Inflammation Rat
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外源性雄激素上调细胞自噬致使大鼠附睾组织损伤
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