Ruboxistaurin对糖尿病大鼠心房重构的影响  

Roles of PKCβ inhibitor Ruboxistaurin on atrial remodeling in diabetic rats

作　　者：王海丽 徐园园 宫孟琦 李健[1] 张跃[1] 程立君[1] 刘长乐[1] 刘彤[1] 李广平[1] 富华颖[1] WANG Hai-li;XU Yuan-yuan;GONG Meng-qi;LI Jian;ZHANG Yue;CHENG Li-jun;LIU Chang-le;LIU Tong;LI Guang-ping;FU Hua-ying.(Department of Cardiology,Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease,Tianjin Institute of Cardiology, Tianjin 300211, China)

机构地区：[1]天津医科大学第二医院心脏科天津市心血管病离子与分子机能重点实验室天津心脏病学研究所,天津300211

出　　处：《中国心脏起搏与心电生理杂志》2018年第3期267-272,共6页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：天津市自然科学基金资助(项目编号:16JCYBJC25000);天津市应用基础与前沿技术研究计划项目资助(项目编号:15JCQNJC10200);天津医科大学第二医院中心实验室青年科研基金项目资助(项目编号:2017ydey17)

摘　　要：目的探讨蛋白激酶C-β(PKCβ)在糖尿病心房颤动(简称房颤)发生中的作用及机制。方法健康成年wistar雄性大鼠64只,分为两部分进行实验,每部分32只大鼠,均随机分为4组:对照组(C组),糖尿病组(DM组),PKCβ抑制剂组(CR组)和糖尿病+PKCβ抑制剂组(DMR组),每组8只。第一部分建立链脲菌素诱导的糖尿病模型,CR组及DMR组大鼠予PKCβ抑制剂(Ruboxistaurin,LY333531)1mg·Kg^(-1)·d^(-1)饲养8周,超声心动图测量左房前后径(LAD),左室舒张末内径(LVEDD),左室收缩末内径(LVESD)和左室射血分数(LVEF);HE染色及Masson染色检测左房细胞形态及心房间质纤维化程度;第二部分建立Langendorff灌流的离体大鼠心脏模型,右房起搏记录房间传导时间(IACT),测定房室传导文氏周长(AVWCL),S1S2刺激测定左房和右房有效不应期(LAERP、RAERP),计算心房不应期的离散度(AERPD)。Burst刺激诱发房颤,观察各组房颤诱发情况。结果与C组相比,DM组干预8周后LAD,LAD差值增大(P均<0.05);与DM组相比,DMR组干预8周后LAD,LAD差值减小(P均<0.05)。与C组相比,DM组大鼠左房肌细胞排列紊乱(P<0.05);与DM组相比,DMR组大鼠左房肌细胞排列整齐(P<0.05)。与C组相比,DM组大鼠左房肌细胞横截面积增大(P<0.05);与DM组相比,DMR组大鼠左房肌细胞横截面积减小(P<0.05)。与C组相比,DM组大鼠左房肌胶原容积分数增大(P<0.05);与DM组相比,DMR组大鼠左房肌胶原容积分数减小(P<0.05)。与C组相比,DM组大鼠IACT延长,LAERP减小,RAERP减小,AERPD增大(P均<0.05);与DM组相比,DMR组IACT缩短,LAERP增大,RAERP增大,AERPD减小(P均<0.05)。与C组相比,DM组大鼠房颤诱发率明显升高(P<0.05);与DM组相比,DMR组大鼠房颤诱发率显著降低(P<0.05)。结论 RBX可以明显减轻糖尿病大鼠左房的纤维化,改善糖尿病导致的电重构,降低了房颤的发生率。Objective To investigate the role and mechanism of protein kinase C disforms beta （PKCβ） in the development of atrial fibrillation in diabetes mellitus by establishing streptozotocin-induced diabetes mellitus and using pathology and electrophysiological methods. Methods Sixty-four healthy adult wistar rats were used for 2 parts of the experiment. The rats of every part were randomly divided into four groups： control group （C-group）,diabetes mellitus group （DM-group）, PKCβ inhibitor group （CR-group） and diabetes mellitus ＋ PKCI3 inhibitor group （DMR-group）, 8 rats in each group. The rats in the first part were used for establishing streptozotocin-in- duced diabetic model. The rats in CR-group and DMR- group were treated with PKCβ inhibitor （Ruboxistaurin,LY333531） for 1 mg· Kg- 1· d-1 for 8 weeks. Left atrial diameter （LAD）, left ventricular end di- astolic diameter （LVEDD）, left ventricular end-dias- tolic diameter （LVESD） and left ventricular ejection fraction （LVEF） were measured by echocardiography;The left atrial myocardial cell size was determined by HE staining and the interstitial collagen volume fraction in LA myocardium was calculated by Masson staining. The rats in the second part were used for cardiac electrophysiology in vitro. The heart models of Langendorff perfused rats were established to use right atrium pacing to measure the interatrial conduction time （IACT）, wenckbach cycle length of AV conduction （AVWCL）.The left atrial effective refractory period （LAERP） ,the right atrial effective refractory period （RAERP） and the atrial effective refractory period dispersion （AERPD） were measured by S1S2 stimulation. The incidence of atrial fibrillation was recorded by burst stimulation in each group. Results Compared with C-group, after 8 weeks＇ intervention in the DM-group the LAD increased and the difference of LAD increased （P〈0.05）. Compared with DM-group, after 8 weekstinter- vention in DMR-group the LAD decreased and the d

关 键 词：心血管病学 心房颤动 糖尿病 蛋白激酶C—β 蛋白激酶C-β抑制剂 重构 信号传导通路 

分 类 号：R541.75[医药卫生—心血管疾病] R587.1[医药卫生—内科学]