肾素前体及其受体通过活性氧产生增多促进人脐动脉平滑肌细胞的增殖
刘峰伊，刘晓云，张丽娇，程云鹏，姜一农
基金项目：高等学校博士学科点专项科研基金（20102105110006） 作者简介：刘峰伊（1984-），女，博士研究生，主要研究方向：动脉粥样硬化 通信联系人：姜一农（1964-），女，教授，主要研究方向：动脉粥样硬化的基础研究.

（大连医科大学附属第一医院心内科，大连，116021）
摘要：肾素(前体)受体(PRR)作为肾素-血管紧张素(RAS)系统的新成员，能够不依赖于血管紧张素II(AngII)发挥作用，使人们对传统的RAS系统有了新的认识。目的：研究肾素前体及其受体对人脐动脉平滑肌细胞(HUASMCs)增殖的影响及其可能的机制。方法：以原代培养的HUASMCs作为研究对象，用肾素前体干预HUASMCs，用流式细胞仪测定活性氧(ROS)的产生，用CCK-8测定细胞的增殖。结果：肾素前体与PRR结合可不依赖于AngII促进HUASMCs的增殖，同时肾素前体与PRR结合可不依赖于AngII可促进ROS产生增多。NADPH氧化酶抑制剂可显著降低肾素前体引起的ROS升高，同时可明显降低由肾素前体引起的HUASMCs的增殖。结论：肾素前体及其受体可不依赖于AngII促进ROS产生增多，并进一步促进HUASMCs的增殖。
关键词：肾素（前体）受体，活性氧，动脉粥样硬化，血管平滑肌细胞增殖
中图分类号：R331.3+6
Binging of prorenin to (pro)renin receptor induces the proliferation of human umbilical artery smooth muscle cells via ROS generation
LIU Fengyi, LIU Xiaoyun, ZHANG Lijiao, CHENG Yunpeng, JIANG Yinong
(Department of Cardiology, The First Affiliated Hospital of Dalian Medical University，Dalian，116021)
Abstract: Since the discovery of (pro)renin receptor (PRR), it has been considered as a novel  bioactive molecule of the renin-angiotensin system (RAS). The activation of PRR can elicit a series of angiotensin II (AngII)-independent effects. Aim: To investigate the effects of prorenin and PRR on the proliferation of human umbilical artery smooth musclecells(HUASMCs) and explore the possible mechanisms underlying these effects. Methods: After stimulation with prorenin, we evaluated the proliferation of the HUASM cells by CCK-8 and the production of  reactive oxygen species (ROS) on a flow cytometer. Results: The binding of prorenin to PRR can promote proliferation independently of AngII in HUASM cells. In addition, the binding of prorenin to PRR can also increase the production of reactive oxygen species (ROS) independently of AngII. The pretreatment of HUASM cells with an NADPH oxidase inhibitor DPI decreased the production of ROS and also significantly attenuated the prorenin-induced proliferation.  Conclusion: Binding of prorenin to PRR can induce HUASM cells proliferation via the ROS generation.
Key words: (pro)renin receptor, ROS, atherosclerosis, proliferation