Tang Jia-Zhen, Xu Wen-Qiong, Wei Fu-Juan, Jiang Yang-Zhen, Zheng Xiao-Xue
Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Exp Ther Med. 2020 Apr;19(4):2895-2900. doi: 10.3892/etm.2020.8539. Epub 2020 Feb 21.
The present study was designed to investigate the role of nicotinamide phosphoribosyltransferase (Nampt) overexpression in a rat model of Hashimoto's thyroiditis (HT) and its mechanism of action. A rat model of HT was constructed, and the HT rats were injected with an adenoviral expression vector carrying the gene. The expression of Nampt and Toll-like receptor 4 (TLR4) in thyroid tissues was examined using immunohistochemistry (IHC), RT-qPCR and western blot analyses. Serum anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured using chemiluminescence method. Hematoxylin and eosin (H&E) and IHC staining of the rat thyroid tissues showed destroyed thyroid follicles and monocyte infiltration, as well as increased Nampt expression in the thyroid tissues of rats with HT. Furthermore, it was found that Nampt overexpression led to increased severity of inflammatory infiltration in thyroid tissues and increased levels of TPOAb in the serum of HT rats; however, the serum TGAb level was not affected by Nampt overexpression. In addition, Nampt overexpression promoted TLR4 expression in HT rats. In conclusion, it was demonstrated that Nampt was strongly expressed in the capillary region of HT rats thyroid tissues. The mRNA level was increased but the Nampt protein level was decreased in the thyroid tissues of rats with HT. Nampt overexpression has a promotive effect on HT progression, and this effect was related to TLR4. This study suggests that inhibition of Nampt activity may be valuable in the treatment of HT.
本研究旨在探讨烟酰胺磷酸核糖转移酶（Nampt）过表达在桥本甲状腺炎（HT）大鼠模型中的作用及其作用机制。构建HT大鼠模型，并向HT大鼠注射携带该基因的腺病毒表达载体。采用免疫组织化学（IHC）、RT-qPCR和蛋白质免疫印迹分析检测甲状腺组织中Nampt和Toll样受体4（TLR4）的表达。采用化学发光法检测血清抗甲状腺球蛋白抗体（TGAb）和抗甲状腺过氧化物酶抗体（TPOAb）。苏木精-伊红（H&E）染色和大鼠甲状腺组织的IHC染色显示甲状腺滤泡破坏和单核细胞浸润，以及HT大鼠甲状腺组织中Nampt表达增加。此外，发现Nampt过表达导致甲状腺组织炎症浸润严重程度增加，HT大鼠血清中TPOAb水平升高；然而，血清TGAb水平不受Nampt过表达的影响。此外，Nampt过表达促进HT大鼠中TLR4的表达。总之，证明Nampt在HT大鼠甲状腺组织的毛细血管区域强烈表达。HT大鼠甲状腺组织中Nampt mRNA水平升高，但Nampt蛋白水平降低。Nampt过表达对HT进展有促进作用，且这种作用与TLR4有关。本研究表明抑制Nampt活性可能对HT治疗有价值。
