DIZE对糖尿病心肌病大鼠心功能的保护作用  

Protective effect of DIZE on heart function of rats with diabetic cardiomyopathy

作　　者：杨旻[1,2] 曹新冉[2] 王园园 王晓琼[2] 于诗然[2] 董波 高靖[1,3] YANG Min;CAO Xinran;WANG Yuanyuan;WANG Xiaoqiong;YU Shiran;DONG Bo;GAO Jing(Shandong University of Traditional Chinese Medicine, Jinan 250014, China;Department of Cardiology, Shandong Provincial Hospital, Jinan 250021, China;Department of Pathology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China)

机构地区：[1]山东中医药大学,山东济南250014 [2]山东省立医院心内科,山东济南250021 [3]山东中医药大学第二附属医院病理科,山东济南250001

出　　处：《中国病理生理杂志》2018年第1期147-151,177,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81170207)

摘　　要：目的:观察研究血管紧张素转换酶2(ACE2)激动剂重氮氨苯脒乙酰甘氨酸盐(DIZE)对糖尿病心肌病(DCM)大鼠心功能的保护作用。方法:30只健康雄性Wistar大鼠随机分为正常对照组、DCM组和DIZE处理组(DIZE组),每组10只。DCM组与DIZE组一次性腹腔注射链脲佐菌素65 mg/kg,建立糖尿病模型,12周后经超声检查选出符合糖尿病心肌病的大鼠模型,分别给予DIZE 15 mg·kg^(-1)·d^(-1)或等体积生理盐水,皮下泵入给药4周处理。第16周末行超声检测心功能后麻醉处死大鼠。通过HE染色和Masson染色观察大鼠心肌组织形态学变化,Wsetern blot、ELISA和免疫组化等方法观察ACE2、血管紧张素(Ang)Ⅱ、Ang-(1-7)、白细胞介素(IL)-1、IL-6和结缔组织生长因子(CTGF)等指标的变化。结果:DIZE显著提高了糖尿病大鼠心肌中ACE2的表达,DIZE组较DCM组心肌组织中胶原含量明显降低,IL-1和IL-6蛋白表达水平明显下降,心功能得到明显改善(P<0.05)。结论:ACE2内源性激动剂DIZE显著提高了ACE2的水平,降低了炎症水平,从而对DCM大鼠心功能起到保护作用。AIM:To observed the protective effect of diminazene aceturate(DIZE),an angiotensin-converting enzyme2(ACE2)activator,on rats with diabetic cardiomyopathy(DCM).METHODS:Male Wistar rats(n=30)were randomly divided into normal control group,DCM group and DIZE treatment group(DIZE group).The rats in DCM group and DIZE group were intraperitoneally injected with streptozotocin(65mg/kg)to establish diabetic model.After12weeks,the diabetic rats were infused with DIZE at15mg·kg-1·d-1or the same volume of saline for4weeks using osmotic minipump.The cardiac function was measured at the end of the16th week.The methods of Mason staining and HE staining were used to observe the morphological changes of the myocardial tissue.Western blot,ELISA and immunohistochemistry were used to observe the changes of ACE2,angiotensin(Ang)Ⅱ,Ang-(1-7),interleukin(IL)-1,IL-6and connective tissue growth factor(CTGF).RESULTS:DIZE significantly improved the expression of ACE2in diabetic rats(P<0.05).Compared with DCM group,the levels of IL-1and IL-6in DIZE group were significantly decreased,and the cardiac function in DIZE group was significantly improved(P<0.05).CONCLUSION:ACE2endogenous agonist DIZE significantly increases the ACE2level and reduces the level of inflammation,thus protecting the heart function of DCM rats.

关 键 词：糖尿病心肌病 血管紧张素转换酶 重氮氨苯脒乙酰甘氨酸盐 炎症 心功能 

分 类 号：R587.2[医药卫生—内分泌] R363.2[医药卫生—内科学]