Department of Cardiovascular Medicine, Xingtai People's Hospital, No.16 Hongxing East Street, Qiaodong District, Xingtai, 054000, Hebei, China.
Eur J Med Res. 2020 Mar 17;25(1):3. doi: 10.1186/s40001-020-00404-7.
The aim of the study is to investigate the effects of miR-34a targeted at PAI-1 on urinary microalbumin and renal function in hypertensive mice.
Twenty specific-pathogen-free (SPF) BPN/3J mice were selected in normal group, and 120 SPF BPH/2J mice were evenly divided into model group, negative control group, miR-34a mimic group, miR-34a inhibitor group, Si-PAI-1 group, and miR-34a inhibitor + Si-PAI-1 group. qRT-PCR was used to detect the expression of miR-34a and PAI-1 mRNA. The protein expressions of PAI-1, angiotensin-converting enzyme (ACE) and ACE2 were detected by Western blot. Serum levels of AngII and Ang1-7 were detected by ELISA.
miR-34a negatively regulated the expression of PAI-1. Compared with the normal group, mice in the other groups had significantly lower body weight, increased systolic blood pressure and 24-h urinary microalbumin content, decreased miR-34a expression, superoxide dismutase (SOD) and nitric oxide (NO) content, and ACE2 protein expression, and increased PAI-1 expression, serum creatinine (Scr), blood urea nitrogen (BUN) malondialdehyde (MDA), AngII and Ang1-7 levels, and ACE protein expression (all P < 0.05). Compared with the model group, mice in the miR-34a mimic group and Si-PAI-1 group had no significant changes in body weight (all P > 0.05), while they had significantly lower systolic blood pressure and 24-h urinary microalbumin content, increased SOD and NO levels and ACE2 protein expression, and decreased PAI-1 expression, Scr, BUN, MDA, AngII and Ang1-7 levels, and ACE protein expression (all P < 0.05). Compared with the miR-34a inhibitor group, symptoms in miR-34a inhibitor + Si-PAI-1 group were significantly improved (all P < 0.05).
miR-34a can inhibit the expression of PAI-1, thereby reducing urinary microalbumin content in hypertensive mice and protecting their renal function.
本研究旨在探讨靶向 PAI-1 的 miR-34a 对高血压小鼠尿微量白蛋白和肾功能的影响。
选择 20 只特定病原体（SPF）BPN/3J 小鼠作为正常组，将 120 只 SPF BPH/2J 小鼠平均分为模型组、阴性对照组、miR-34a 模拟物组、miR-34a 抑制剂组、Si-PAI-1 组和 miR-34a 抑制剂+Si-PAI-1 组。qRT-PCR 检测 miR-34a 和 PAI-1 mRNA 的表达。Western blot 检测 PAI-1、血管紧张素转换酶（ACE）和 ACE2 的蛋白表达。ELISA 检测血清 AngII 和 Ang1-7 水平。
miR-34a 负调控 PAI-1 的表达。与正常组相比，其他组小鼠体重明显降低，收缩压和 24 小时尿微量白蛋白含量升高，miR-34a 表达、超氧化物歧化酶（SOD）和一氧化氮（NO）含量、ACE2 蛋白表达降低，PAI-1 表达、血清肌酐（Scr）、血尿素氮（BUN）、丙二醛（MDA）、AngII 和 Ang1-7 水平、ACE 蛋白表达升高（均 P<0.05）。与模型组相比，miR-34a 模拟物组和 Si-PAI-1 组小鼠体重无明显变化（均 P>0.05），收缩压和 24 小时尿微量白蛋白含量降低，SOD 和 NO 水平及 ACE2 蛋白表达升高，PAI-1 表达、Scr、BUN、MDA、AngII 和 Ang1-7 水平、ACE 蛋白表达降低（均 P<0.05）。与 miR-34a 抑制剂组相比，miR-34a 抑制剂+Si-PAI-1 组症状明显改善（均 P<0.05）。
miR-34a 可抑制 PAI-1 的表达，从而降低高血压小鼠尿微量白蛋白含量，保护其肾功能。
