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褪黑素处理的间充质干细胞在改善胺碘酮引起的甲状腺损伤中的优先级。对凋亡途径的深入观察。

The priority of mesenchymal stem cells treated with melatonin in ameliorating thyroid impairment induced by amiodarone. Thorough look on the apoptotic pathway.

机构信息

Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt.

Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt.

出版信息

Pathol Res Pract. 2024 Mar;255:155212. doi: 10.1016/j.prp.2024.155212. Epub 2024 Feb 17.

DOI:10.1016/j.prp.2024.155212
PMID:38412657
Abstract

Amiodarone treatment has been associated with thyroid alterations. This work was planned to consider therapeutic outcome of MSCs versus MSCs treated with melatonin in minimizing amiodarone -induced deviations in thyroid. We handed-down 50 male Wistar rats, then distributed them into 5 groups; I, II, III, IV, V; control, sham control, amiodarone treated, amiodarone and MSCs treated, and amiodarone, MSCs and melatonin treated groups respectively. Light microscopic examination; levels of T3, T4 and TSH, Oxidative/antioxidative tissue markers, immune-histochemical staining (Bcl2, BAX, iNOS) and real time PCR (IL-6 and VEGF and Caspase 3) were done. Results of group III showed degenerated follicles, decreased follicular cell count and diminished colloid. Some of the follicles were dilated with signs of inflammatory response and apoptosis. Increased collagen deposition in group III was marked. The positive immune-reactive cells of Bcl-2 was decreased and that of BAX and iNOS was increased, also T3 and T4 levels were significantly decreased, but TSH was significantly increased in group III comparing it to the group I. There were highly significant diminution in both SOD and GPx and upsurge in MDA intensities in groups III, IV when correlated to the control. In group IV and V the aforementioned values were restored. The PCR results showed significant increase in IL-6 and VEGF and Caspase 3 in group III compared to the control one, whereas, their values in groups IV and V were reestablished. It is concluded that stem cells can to a great extent ameliorate the thyroid damage induced by amiodarone.But, Adding melatonin to the stem cells culture was found to have auxiliary beneficial effect in the improving the thyroid structure and function.

摘要

胺碘酮治疗与甲状腺改变有关。本研究旨在观察间充质干细胞(MSCs)与褪黑素处理后的 MSCs 治疗在最小化胺碘酮诱导的甲状腺偏差方面的治疗效果。我们传代培养了 50 只雄性 Wistar 大鼠,然后将它们分为 5 组:I、II、III、IV、V;对照组、假手术对照组、胺碘酮处理组、胺碘酮和 MSCs 处理组、胺碘酮、MSCs 和褪黑素处理组。进行了光镜检查;检测 T3、T4 和 TSH 水平、氧化/抗氧化组织标志物、免疫组织化学染色(Bcl2、BAX、iNOS)和实时 PCR(IL-6、VEGF 和 Caspase 3)。结果显示,第 III 组的滤泡退化,滤泡细胞计数减少,胶体减少。一些滤泡扩张,伴有炎症反应和细胞凋亡的迹象。第 III 组的胶原沉积增加。Bcl-2 的阳性免疫反应细胞减少,BAX 和 iNOS 的阳性免疫反应细胞增加,T3 和 T4 水平也显著降低,但 TSH 水平显著升高。与对照组相比,第 III 组的 SOD 和 GPx 显著降低,MDA 强度显著升高。第 IV 组和第 V 组的上述值得到恢复。PCR 结果显示,第 III 组的 IL-6、VEGF 和 Caspase 3 显著高于对照组,而第 IV 组和第 V 组的这些值得到恢复。结论:间充质干细胞在很大程度上可以改善胺碘酮引起的甲状腺损伤。然而,在间充质干细胞培养中添加褪黑素被发现对改善甲状腺结构和功能有辅助有益的作用。

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