Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, China.
Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, China.
Int Immunopharmacol. 2018 Feb;55:1-8. doi: 10.1016/j.intimp.2017.11.043. Epub 2017 Dec 5.
Renal fibrosis yields decreased renal function and is a potent contributor to chronic kidney disease (CKD). Telbivudine (LdT) is an anti-hepatitis B virus (HBV) drug that has been found to steadily improve renal function, but the mechanism of drug action is unclear. One explanation is that LdT impacts inflammatory or fibrotic pathways. In this study, we investigated renal protection by LdT in a rat model of unilateral ureteral obstruction (UUO). UUO rats received oral gavage of LdT (1, 1.5, or 2g/kg/day) for 5weeks. Kidney tissues were examined histopathologically with hematoxylin and eosin and Masson's trichrome stain. To assess proliferation of myofibroblasts and matrix accumulation, α-smooth muscle actin (α-sma) and collagen type I and III were detected. Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-α were evaluated as a measure of proinflammatory cytokines. Transforming growth factor (TGF)-β and nuclear factor-κB (NF-κB) were considered the canonical signaling components in our investigation of the underlying mechanism of LdT action. Histopathology results indicated that LdT ameliorates renal injury and matrix accumulation. Expression of α-sma and collagen I/III as well as key fibrotic signaling factors in the TGF-β/Smad pathway were downregulated. In addition, LdT suppressed the release of IL-1 and TNF-α and decreased the expression of NF-κB by inhibiting toll-like receptor 4. Taken together, these findings indicate that LdT can attenuate renal fibrosis and inflammation via TGF-β/Smad and NF-κB pathways in UUO.
肾纤维化导致肾功能下降，是慢性肾脏病（CKD）的主要原因。替比夫定（LdT）是一种抗乙型肝炎病毒（HBV）药物，已被发现可稳定改善肾功能，但药物作用机制尚不清楚。一种解释是 LdT 影响炎症或纤维化途径。在这项研究中，我们在单侧输尿管梗阻（UUO）大鼠模型中研究了 LdT 的肾脏保护作用。UUO 大鼠接受 LdT（1、1.5 或 2g/kg/天）口服灌胃 5 周。用苏木精和伊红及 Masson 三色染色法对肾脏组织进行组织病理学检查。为了评估肌成纤维细胞增殖和基质积累，检测了α-平滑肌肌动蛋白（α-sma）和胶原 I 和 III。白细胞介素 1（IL-1）和肿瘤坏死因子（TNF）-α作为促炎细胞因子的指标进行评估。转化生长因子（TGF）-β和核因子-κB（NF-κB）被认为是我们研究 LdT 作用机制的经典信号成分。组织病理学结果表明，LdT 可改善肾脏损伤和基质积累。α-sma 和胶原 I/III 的表达以及 TGF-β/Smad 途径中的关键纤维化信号因子下调。此外，LdT 通过抑制 Toll 样受体 4 抑制 IL-1 和 TNF-α的释放并降低 NF-κB 的表达。综上所述，这些发现表明 LdT 可通过 TGF-β/Smad 和 NF-κB 途径减轻 UUO 中的肾脏纤维化和炎症。
