Wang Li-Ping, Fan Su-Jing, Li Shu-Min, Wang Xiao-Jun, Sun Na
Department of Physiology; Tangshan Key Laboratory for Preclinical on Chronic Diseases, School of Basic Medicine, North China University of Science and Technology, Tangshan 063000, China.
Sheng Li Xue Bao. 2016 Oct 25;68(5):684-690.
The purpose of the present study is to explore the effect of aliskiren on the proliferation of cardiac fibroblasts (CFs) in AGT-REN double transgenic hypertensive (dTH) mice. The cultured CFs from AGT-REN dTH mice were divided into AGT-REN group (dTH) and aliskiren group (ALIS). Cultured CFs from C57B6 mice were served as control (WT). The effect of different concentration of aliskiren (1 × 10, 1 × 10, 1 × 10, 1 × 10 mol/L) on CFs proliferation was determined by MTT assay. After treatment with 1 × 10 mol/L aliskiren for 24 h, α-SMA, collagen I, III and NADPH oxidase (NOX) protein expression in CFs of AGT-REN dTH mice were detected by Western blot. The collagen synthesis in CFs was assessed by hydroxyproline kit. The expression of ROS was determined by DHE. Results showed that the blood pressure and plasma Ang II levels were significantly increased and CFs proliferation was significantly increased as well in AGT-REN dTH mice compared with WT group. However, aliskiren intervention decreased CFs proliferation, myofibroblast transformation, as well as the collagen I and III synthesis in CFs of AGT-REN dTH mice. Meanwhile, aliskiren inhibited ROS content and NOX2/NOX4 protein expression in CFs of AGT-REN dTH mice. These results suggest that aliskiren decreases the cell proliferation, myofibroblast transformation and collagen production in CFs of AGT-REN dTH mice, which might be through inhibition of oxidative stress response.
本研究的目的是探讨阿利吉仑对AGT-REN双转基因高血压（dTH）小鼠心脏成纤维细胞（CFs）增殖的影响。将AGT-REN dTH小鼠培养的CFs分为AGT-REN组（dTH）和阿利吉仑组（ALIS）。将C57B6小鼠培养的CFs作为对照（WT）。采用MTT法测定不同浓度阿利吉仑（1×10、1×10、1×10、1×10 mol/L）对CFs增殖的影响。用1×10 mol/L阿利吉仑处理24小时后，通过蛋白质免疫印迹法检测AGT-REN dTH小鼠CFs中α-SMA、I型胶原、III型胶原和NADPH氧化酶（NOX）蛋白的表达。通过羟脯氨酸试剂盒评估CFs中的胶原合成。用DHE测定ROS的表达。结果显示，与WT组相比，AGT-REN dTH小鼠的血压和血浆Ang II水平显著升高，CFs增殖也显著增加。然而，阿利吉仑干预降低了AGT-REN dTH小鼠CFs的增殖、肌成纤维细胞转化以及CFs中I型和III型胶原的合成。同时，阿利吉仑抑制了AGT-REN dTH小鼠CFs中的ROS含量和NOX2/NOX4蛋白表达。这些结果表明，阿利吉仑可降低AGT-REN dTH小鼠CFs的细胞增殖、肌成纤维细胞转化和胶原生成，这可能是通过抑制氧化应激反应实现的。
