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目的:评估糖尿病和甲状腺功能亢进对雄性动物睾丸和附睾组织形态学及类固醇激素合成的影响,并初步探讨其作用机制。创新点:以小鼠为模型,首次研究并发糖尿病和甲状腺功能亢进对雄性哺乳动物睾丸、附睾发育和类固醇激素合成的影响。方法:32只ICR品系小鼠分为四组:对照组(C)、糖尿病组(D)、糖尿病+甲亢组(DH)和甲亢组(H)。D组小鼠以200 mg/kg剂量单次腹膜内注射链脲佐菌素(STZ),诱导糖尿病成功。另对其中一半以0.3 mg/kg剂量每天注射甲状腺素,组成DH组。小鼠试验结束后,采集睾丸、附睾和血液,并离心分离获得血清。睾丸和附睾用4%(0.04 g/ml)多聚甲醛固定,并用苏木精-伊红染色法(H&E)观察睾丸和附睾组织形态学变化,用放射免疫测定(RIA)试剂盒检测血清中睾酮、促甲状腺激素(TSH)、胰岛素、甲状腺素(T4)和三碘甲状腺原氨酸(T3)的含量并进行分析。结论:D和DH组小鼠的体重、睾丸和附睾的重量显著降低。相比于正常甲亢或糖尿病小鼠,DH组中血糖水平显著升高。甲状腺激素可能是通过改变糖尿病患者的血清血糖水平对血糖稳态产生瞬时影响。组织形态学分析结果显示,在DH和H组小鼠睾丸中,输精管管腔增大,上皮厚度减少,睾丸生殖干细胞发生萎缩性变化。DH组小鼠的附睾头呈现主细胞压实、纤毛、脂质空泡化和炎症浸润现象。在附睾尾部观察到了小管完整性受损、透明细胞聚积和细胞脱落,并发现圆形精子。对于DH和H组,甲亢提高了小鼠血清睾酮水平,并损害了附睾的组织形态。总之,本试验模拟了多腺体自身免疫综合征对雄性繁殖的影响,这将有助于更好地了解男性并发糖尿病和甲亢患者不育的原因。
Objective: To evaluate the effects of diabetes and hyperthyroidism on histomorphology of testis and epididymis and the synthesis of steroid hormones in male animals, and to explore its mechanism. Innovative point: The mouse model, the first study of concomitant diabetes and hyperthyroidism on male mammalian testes, epididymis development and steroid hormone synthesis. Methods: 32 ICR mice were divided into four groups: control group (C), diabetes group (D), diabetes + hyperthyroidism group (DH) and hyperthyroidism group (H). Group D mice were given a single intraperitoneal injection of streptozotocin (STZ) at a dose of 200 mg / kg to induce successful diabetes mellitus. In addition, half of them were injected with thyroxine at a dose of 0.3 mg / kg daily to form DH group. After the mice were tested, testis, epididymis and blood were collected and centrifuged to obtain serum. The testis and epididymis were fixed with 4% (0.04 g / ml) paraformaldehyde and histomorphology of testis and epididymis was observed by hematoxylin-eosin staining (H & E). Serum levels were measured by radioimmunoassay (RIA) The levels of testosterone, thyrotropin (TSH), insulin, thyroxine (T4) and triiodothyronine (T3) were analyzed and analyzed. Conclusion: The body weight, testis and epididymis weight of mice in D and DH groups were significantly decreased. Compared to normal hyperthyroidism or diabetic mice, DH group significantly increased blood glucose levels. Thyroid hormones may have a transient effect on blood glucose homeostasis by altering the serum glucose level in diabetics. Histomorphological analysis showed that in the testes of DH and H mice, the lumen of vas deferens increased, the thickness of epithelial cells decreased, and the atrophic changes of testicular germ cells occurred. The epididymis of DH group showed the main cell compaction, cilia, lipid vacuolization and inflammatory infiltration. Tubular integrity damage, clear cell accumulation and cell shedding were observed at the caudal epididymis and round sperm was found. For DH and H groups, hyperthyroidism increased serum testosterone levels in mice and damaged the morphology of the epididymis. In summary, this trial simulated the effects of polyglandular autoimmune syndrome on male reproduction, which will help to better understand the causes of infertility in men with diabetes and hyperthyroidism.