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脂肪组织间充质干细胞来源的胰岛素生成细胞对糖尿病大鼠睾丸功能障碍的影响。

Impact of insulin producing cells derived from adipose tissue mesenchymal stem cells on testicular dysfunction of diabetic rats.

作者信息

Abd El Kader Mai A, Gabr Mahmoud M, Khater Sherry M, Ghanem Reham A, Abou El Naga Amoura M

机构信息

Department of Biotechnology, Urology and Nephrology Center, Mansoura, Egypt.

Department of Pathology, Urology and Nephrology Center, Mansoura, Egypt.

出版信息

Heliyon. 2021 Nov 1;7(11):e08316. doi: 10.1016/j.heliyon.2021.e08316. eCollection 2021 Nov.

Abstract

The present study is to clarify the effect of insulin-producing cells (IPCs) derived from adipose tissue mesenchymal stem cells (AT-MSCs) on diabetic-induced impairments as the abnormalities of testicular tissues, oxidative stress of testes, and defects of spermatogenesis. Diabetes was stimulated by streptozotocin (STZ) injection in male adult Sprague Dawley (SD) rats. Diabetes was confirmed by taking two highly consecutive fasting blood sugar readings; more than 300 mg/dl; within one week. Five million of IPCs derived from AT-MSCs; encased in TheraCyte capsule; were then directly transplanted (one implant for each rat) subcutaneously in diabetic rats. Implants were maintained for 3 months and the fasting blood sugar of the transplanted rats was observed every month. At the end of the experiment; serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also estimated. The sperm parameters (count, motility, and abnormality) were recorded. In testicular tissue; GPX4, Bcl2, and Bax levels were evaluated, while oxidative stress and antioxidant enzymes activities were measured in the testes homogenate. Also, histopathological alterations were examined in the testes cross-section. In the results, it was found that IPCs treatment enhanced the serum testosterone, FSH, and LH levels. Diabetic-induced impairments in the sperm parameters were noticeably improved post-IPCs transplantation in the diabetic rats. Moreover, the treatment improved the diabetic-associated testicular oxidative stress. Also, it was recognized that the Bax expression decreased, while, GPX4 and Bcl2 expression increased in the treated rats. Meanwhile, the abnormalities showed in the histopathological studies of the hyperglycemic rat's testes were attenuated post-treatment. So, IPCs transplantation improved diabetes and consequently protected against hyperglycemia-induced testicular damages.

摘要

本研究旨在阐明脂肪组织间充质干细胞(AT-MSCs)来源的胰岛素生成细胞(IPCs)对糖尿病诱导的睾丸组织异常、睾丸氧化应激和精子发生缺陷等损伤的影响。通过给成年雄性Sprague Dawley(SD)大鼠注射链脲佐菌素(STZ)诱导糖尿病。在一周内连续两次空腹血糖读数超过300mg/dl来确诊糖尿病。将500万个源自AT-MSCs的IPCs包裹在TheraCyte胶囊中,然后直接皮下移植到糖尿病大鼠体内(每只大鼠植入一个)。植入物维持3个月,每月观察移植大鼠的空腹血糖。实验结束时,还测定了血清睾酮、促卵泡激素(FSH)和促黄体生成素(LH)。记录精子参数(数量、活力和异常情况)。在睾丸组织中,评估GPX4、Bcl2和Bax水平,同时在睾丸匀浆中测量氧化应激和抗氧化酶活性。此外,检查睾丸横截面的组织病理学改变。结果发现,IPCs治疗提高了血清睾酮、FSH和LH水平。糖尿病大鼠移植IPCs后,糖尿病诱导的精子参数损伤明显改善。此外,该治疗改善了糖尿病相关的睾丸氧化应激。还发现,治疗组大鼠的Bax表达降低,而GPX4和Bcl2表达增加。同时,高血糖大鼠睾丸组织病理学研究中显示的异常在治疗后减轻。因此,IPCs移植改善了糖尿病,从而预防了高血糖诱导的睾丸损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a87f/8601995/c91fca59a7f4/gr1.jpg

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