El Agaty Sahar M
Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Can J Physiol Pharmacol. 2018 Jun;96(6):603-610. doi: 10.1139/cjpp-2017-0252. Epub 2018 Feb 6.
This study was designed to investigate whether and how triiodothyronine (T) affects renal function in an experimental model of chronic kidney disease. Twenty-four female rats were divided into the following groups: sham-operated control group (n = 8), 5/6 nephrectomized group (Nx, n = 8), and 5/6 nephrectomized group treated with T for 2 weeks (T-Nx, n = 8). T administration significantly decreased serum levels of urea, creatinine, tumour necrosis factorα, and interleukin-6 compared with serum levels in the Nx group. The levels of malondialdehyde, transforming growth factor β, fibronectin, and collagen IV, as well as the expression of inducible nitric oxide synthase, nuclear factor κB, poly(ADP-ribose) polymerase, caspase-3, and Bax were all significantly decreased, though not normalized, in the remnant kidney of rats in the T-Nx group compared with Nx rats. Glutathione, heme oxygenase-1 levels, as well as endothelial nitric oxide synthase expression were increased in the remnant kidney of the T-Nx group. Histological studies revealed focal necrosis of renal tubules associated with inflammatory cell infiltration and fibrosis in the Nx group. These changes were alleviated in T-Nx rats. This study showed that T administration attenuated the clinical and histological signs of renal injury in 5/6 nephrectomized rats by mitigating renal oxidative stress, inflammation, apoptosis, and fibrosis.
本研究旨在探讨在慢性肾脏病实验模型中三碘甲状腺原氨酸(T)是否以及如何影响肾功能。24只雌性大鼠被分为以下几组:假手术对照组(n = 8)、5/6肾切除组(Nx,n = 8)以及5/6肾切除并接受T治疗2周的组(T-Nx,n = 8)。与Nx组相比,给予T显著降低了血清尿素、肌酐、肿瘤坏死因子α和白细胞介素-6水平。与Nx大鼠相比,T-Nx组大鼠残余肾中丙二醛、转化生长因子β、纤连蛋白和IV型胶原水平以及诱导型一氧化氮合酶、核因子κB、聚(ADP-核糖)聚合酶、半胱天冬酶-3和Bax的表达均显著降低,虽未恢复正常。T-Nx组残余肾中谷胱甘肽、血红素加氧酶-1水平以及内皮型一氧化氮合酶表达增加。组织学研究显示,Nx组肾小管局灶性坏死伴有炎性细胞浸润和纤维化。这些变化在T-Nx大鼠中得到缓解。本研究表明,给予T可通过减轻肾脏氧化应激、炎症、细胞凋亡和纤维化,减轻5/6肾切除大鼠肾损伤的临床和组织学表现。