Zhu Dan, Zhang Linlin, Cheng Lijuan, Ren Liansheng, Tang Jie, Sun Dianjun
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
Kidney Blood Press Res. 2016;41(1):9-17. doi: 10.1159/000368542. Epub 2016 Jan 8.
BACKGROUND/AIMS: We aimed to evaluate whether pancreatic kininogenase (PKase) can relieve renal fibrosis and investigate its mechanisms in diabetic nephropathy (DN) rats Methods: We established streptozotocin (STZ) induced-DN rats. After treatment with PKase for 4 weeks, urinary weight, urinary protein content and blood glucose concentration were detected, and then renal histopathological changes were examined using Hematoxylin and Eosin (H&E) and Masson's thrchrome staining. In addition, the expressions of miR-433, transforming growth factor-β1 (TGF-β1) and antizyme inhibitor 1 (Azin1) were detected by qRT-PCR and/or western blotting.
PKase reduced urinary weight, urinary protein contents and blood glucose concentrations. PKase treated DN rats exhibited less renal fibrosis than untreated DN rats (P < 0.05). Furthermore, the expression levels of TGF-β and miR-433 were reduced (P < 0.05), while Azin1 expression was increased in renal tissues of PKase treated DN rats compared with untreated DN rats (P < 0.05).
PKase might not only inhibit the development of DN by reducing urinary weight, urinary protein content and blood glucose concentration in DN rats, but also relieve renal fibrosis in DN rats through inhibiting the expression of TGF-β1, and miR-433 and Azin1 might involve in this process.
背景/目的：我们旨在评估胰激肽原酶（PKase）是否能缓解肾纤维化，并研究其在糖尿病肾病（DN）大鼠中的作用机制。方法：我们建立了链脲佐菌素（STZ）诱导的DN大鼠模型。用PKase治疗4周后，检测尿重量、尿蛋白含量和血糖浓度，然后用苏木精和伊红（H&E）及Masson三色染色法检查肾脏组织病理学变化。此外，通过qRT-PCR和/或蛋白质印迹法检测miR-433、转化生长因子-β1（TGF-β1）和抗酶抑制剂1（Azin1）的表达。
PKase降低了尿重量、尿蛋白含量和血糖浓度。与未治疗的DN大鼠相比，PKase治疗的DN大鼠肾纤维化程度较轻（P<0.05）。此外，与未治疗的DN大鼠相比，PKase治疗的DN大鼠肾组织中TGF-β和miR-433的表达水平降低（P<0.05），而Azin1表达增加（P<0.05）。
PKase可能不仅通过降低DN大鼠的尿重量、尿蛋白含量和血糖浓度来抑制DN的发展，还可能通过抑制TGF-β1的表达来缓解DN大鼠的肾纤维化，并且miR-433和Azin1可能参与了这一过程。
