Zhou Tian-Biao, Qin Yuan-Han, Li Zheng-Yi, Xu Hui-Ling, Zhao Yan-Jun, Lei Feng-Ying
Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing 530021, China.
Int J Mol Sci. 2012;13(3):2769-2782. doi: 10.3390/ijms13032769. Epub 2012 Mar 1.
This study was performed to investigate the association of prohibitin with renal interstitial fibrosis (RIF) lesion and to explore the association of all-trans retinoic acid (ATRA) treatment with prohibitin expression in RIF rats. Rats were divided into three groups: the sham operation group (SHO), the model group subjected to unilateral ureteral obstruction (UUO), and the model group treated with ATRA (GA). Renal tissues were collected at 14 and 28 days after surgery, and the relevant indicators were detected. In comparison with the SHO group, the RIF index in the UUO group was markedly elevated (p < 0.01), and the RIF index in the GA group was alleviated compared with that in the UUO group (p < 0.01). Compared with the SHO group, the expression of prohibitin (protein or mRNA) in the UUO group was significantly reduced (each p < 0.01). Prohibitin expression in the GA group was markedly increased when compared with that in the UUO (p < 0.01). The expression of TGF-β1 (protein and mRNA), protein expressions of Col-IV, fibronectin, α-SMA and cleaved Caspase-3, ROS generation and cell apoptosis index in the UUO group were markedly higher than those in the SHO group (all p < 0.01), and their expressions in the GA group were markedly down-regulated compared to those in the UUO group (all p < 0.01, respectively). The protein expression of prohibitin was negatively correlated with the RIF index, protein expression of TGF-β1, Col-IV, fibronectin, α-SMA or cleaved Caspase-3, ROS generation and the cell apoptosis index (each p < 0.01). In conclusion, lower expression of prohibitin is associated with the RIF, and ATRA treatment is associated with increased prohibitin, which can prevent the progression of RIF.
本研究旨在探讨抑制素与肾间质纤维化（RIF）病变的关系，并探究全反式维甲酸（ATRA）治疗与RIF大鼠中抑制素表达的关系。将大鼠分为三组：假手术组（SHO）、单侧输尿管梗阻（UUO）模型组和ATRA治疗的模型组（GA）。在手术后14天和28天收集肾组织，并检测相关指标。与SHO组相比，UUO组的RIF指数显著升高（p<0.01），与UUO组相比，GA组的RIF指数有所减轻（p<0.01）。与SHO组相比，UUO组中抑制素（蛋白或mRNA）的表达显著降低（各p<0.01）。与UUO组相比，GA组中抑制素的表达明显增加（p<0.01）。UUO组中转化生长因子-β1（TGF-β1）（蛋白和mRNA）、IV型胶原（Col-IV）、纤连蛋白、α-平滑肌肌动蛋白（α-SMA）和裂解的半胱天冬酶-3的蛋白表达、活性氧（ROS）生成及细胞凋亡指数均显著高于SHO组（均p<0.01），与UUO组相比，它们在GA组中的表达明显下调（分别均p<0.01）。抑制素的蛋白表达与RIF指数、TGF-β1、Col-IV、纤连蛋白、α-SMA或裂解的半胱天冬酶-3的蛋白表达、ROS生成及细胞凋亡指数呈负相关（各p<0.01）。总之，抑制素表达降低与RIF相关，ATRA治疗与抑制素增加相关，这可防止RIF的进展。
