藻酸双酯钠纳米剂型对糖尿病心肌病冠脉微循环血栓调节蛋白表达的影响  

Effect of propylene glycol alginate sodium sulfate nanoparticles on the expression of thrombomodulin in coronary microcirculation of diabetic cardiomyopathy

作　　者：毛拥军 王丽娜[2] 胡松[2] 颜贵英[2] 吴月兰 管华诗[1] MAO Yong-jun;WANG Li-na;HU Song;YAN Gui-ying;WU Yue-lan;GUAN Hua-shi(Key Laboratory of Marine Drugs,Ministry ot Educatlon,Key Laboratory of Glycoscience and Glycotechnology,Shandong Province,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Department of Geriatrics,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,山东省糖科学与糖工程重点实验室,医药学院,山东青岛266003 [2]青岛大学附属医院老年医学科,山东青岛266003

出　　处：《中国海洋药物》2018年第5期60-66,共7页Chinese Journal of Marine Drugs

基　　金：海洋药物教育部重点实验室(中国海洋大学)开放基金项目(KLMD(OUC)201202)资助

摘　　要：目的探讨藻酸双酯钠纳米剂型(PSS-NP)对糖尿病心肌病(DCM)大鼠冠脉微循环血栓调节蛋白(TM)表达的影响及其可能机制。方法 52只雄性Wistar大鼠中随机选取40只,一次性腹腔注射STZ制备DM模型。采用心脏超声于8周后筛选DCM大鼠,将其随机分为空白组、溶媒组、阳性对照组、PSS组、PSSNP组,分别灌胃6周。诱导后16周处死大鼠,计算大鼠的心脏指数。采用HE染色观察心肌组织病理改变;采用ELISA法检测血清TM水平;采用RT-PCR法检测心肌TM-mRNA的表达水平,采用免疫组化法观察心肌TM蛋白表达水平。结果与正常对照组相比,DCM大鼠一般状况不佳,体质量明显减轻(P<0.05),血糖水平明显增高(P<0.05);心功能指标LVEF、FS%、EA比值明显减小(P<0.05),LVEDs、LVEDd明显增大(P<0.05);血清sTM水平、TM-mRNA表达水平明显升高(P<0.05),其中PSS-NP组、阳性对照组水平最低(两者无显著性差异,P>0.05)。免疫组化显示,DCM大鼠较正常对照组心肌TM蛋白阳性表达增强,阳性对照组、PSS组、PSS-NP组经治疗后阳性表达减弱。结论藻酸双酯钠纳米剂型可抑制DCM大鼠TM表达,效果优于传统剂型,对治疗DCM冠脉微循环障碍具有重要价值。Objective To investigate the effect of propylene glycol alginate sodium sulfate nanoparticles (PSS-NP)on the expression of thrombomodulin in streptozotocin (STZ)induced diabetic cardiomyopathy rats and its possible mechanism.Methods 40 rats were selected randomly from 52 male Wistar rats as the model group and the remaining 12 as the control group.Diabetes was induced in 40 male Wistar rats by single intraperitoneal injection of STZ.8 weeks after the STZ injection,echocardiography was applied to select DCM rats by evaluating cardiac function.DCM rats were randomly divided into five groups:blank group,vehicle group,positive coritrol group,propylene glycol alginate sodium sulfate (PSS)group,propylene glycol alginate sodium sulfate group nanoparticles(PSS-NP)group.From then on,NS and corresponding drugs were orally administered to the rats by gavage for 6 Weeks.16 weeks after the induction,pathological changes in myocardial tissue were observed by HE staining;expression of TM protein in myocardial tissue was observed by immunohistochemistry;serum level of TM was detected by ELISA;expression of TM-mRNA in myocardial tissue was detected by RT-PCR.Results Compared with the control group,the DCM group rats were in poor condition,whose body weights were significantly reduced (P<0.05)and blood glucose levels were significantly higher (P<0.05). The cardiac function index-LVEF,FS%and EA ratio were significantly decreased (P<0.05).LVEDs and LVEDd were significantly increased (P<0.05).Serum sTM levels detected by ELISA,expression of TM-mRNA detected by RT-PCR shared the same tendency.Among all groups,the blank group and vehicle group showed the highest expression level (there was no significant difference between them, P>0.05),followed by the PSS group,then the PSS-NP group and positive control group(there was no significant difference between them,P>0.05),the control group showed the lowest expression level. Conclusion Compared with the traditional formulations,propylene glycol alginate sodium sulfate nanoparticles could inh

关 键 词：藻酸双酯钠 纳米粒 糖尿病心肌病 冠脉微循环 血栓调节蛋白 

分 类 号：R965[医药卫生—药理学]