[1]于鲁彦,胡怡,冯文静,等. 藻酸双酯钠纳米剂型对STZ诱导糖尿病心肌病大鼠胸主动脉内皮损伤的影响[J].青岛大学学报(医学版),2018,54(03 ):277-281.[doi:10.11712/jms201803006]
 YU Luyan,HU Yi,FENG Wenjing,et al. EFFECT OF PSS-LOADED NANOPARTICLES ON ENDOTHELIAL INJURY OF THE THORACIC AORTA IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETIC CARDIOMYOPATHY[J].JOURNAL OF QINGDAO UNIVERSITY (MEDICAL SCIENCES),2018,54(03 ):277-281.[doi:10.11712/jms201803006]
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 藻酸双酯钠纳米剂型对STZ诱导糖尿病心肌病大鼠胸主动脉内皮损伤的影响()
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《青岛大学学报(医学版)》[ISSN:2096-5532/CN:37-1217/R]

卷:
第54卷
期数:
2018年03 期
页码:
277-281
栏目:
出版日期:
2018-05-29

文章信息/Info

Title:
 EFFECT OF PSS-LOADED NANOPARTICLES ON ENDOTHELIAL INJURY OF THE THORACIC AORTA IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETIC CARDIOMYOPATHY
作者:
 于鲁彦胡怡冯文静安妮娜毛拥军
 青岛大学附属医院老年医学科,山东 青岛 266003
Author(s):
 YU Luyan HU Yi FENG Wenjing AN Ni′na MAO Yongjun
 Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
关键词:
 藻酸盐纳米粒子剂型糖尿病心肌病内皮血管大鼠
Keywords:
 alginates nanoparticles dosage forms diabetic cardiomyopathies endothelium vascular rats
分类号:
R5871.2;R916.3
DOI:
10.11712/jms201803006
文献标志码:
A
摘要:
 目的 研究藻酸双酯钠纳米剂型(PSS-NP)对糖尿病心肌病(DCM)大鼠胸主动脉内皮损伤的影响。
方法 将SD大鼠随机分为正常对照(Control)组和糖尿病(DM)组,DM组采用一次性腹腔注射链脲佐菌素(STZ)的方法建立1型DM大鼠模型。诱导8周后将DCM模型制备成功的大鼠随机分为DCM组、DCM+前列地尔(PGE1)组、DCM+低分子肝素(LMWH)组、DCM+PSS组及DCM+PSS-NP组,各给药组分别给予PGE1 5 μg?kg-1?d-1、LMWH 150 U?kg-1?d-1、PSS 20 mg?kg-1?d-1及PSS-NP 20 mg?kg-1?d-1腹腔注射,Control组及DCM组给予等量生理盐水腹腔注射。给药4周后,采用苏木精-伊红(HE)染色观察胸主动脉病理改变,ELISA法检测胸主动脉血管内皮细胞蛋白C受体(PROCR)浓度,Western Blot法检测胸主动脉磷脂酰肌醇-3激酶(PI3K)-p85、血管内皮生长因子A(VEGFA)蛋白的表达及内皮型一氧化氮合酶(eNOS)、蛋白激酶B(Akt)磷酸化水平。
结果 HE染色显示,DCM组大鼠胸主动脉内膜不规则,内皮细胞破坏,细胞核大小不一,PSS-NP可显著改善DCM大鼠胸主动脉内皮形态。ELISA检测显示,DCM组PROCR浓度较Control组显著降低,各给药组PROCR浓度较DCM组均显著增高,以DCM+PSS-NP组增高最明显(F=16.03,P<0.01)。Western Blot检测显示,DCM组PI3K-p85、VEGFA蛋白表达及Akt、eNOS磷酸化水平均较Control组显著降低,各给药组PI3K-p85、VEGFA蛋白表达及Akt、eNOS磷酸化水平均较DCM组显著增高,以DCM+PSS-NP组增高最明显(F=10.06~14.13,P<0.01)。
结论 PSS-NP可能通过上调PI3K/Akt/eNOS/VEGFA信号通路改善STZ诱导的DCM大鼠胸主动脉内皮损伤。
Abstract:
 Objective To investigate the effect of propylene glycol alginate sodium sulfate-loaded nanoparticles (PSS-NP) on endothelial injury of the thoracic aorta in rats with diabetic cardiomyopathy (DCM).
Methods Sprague-Dawley rats were randomly divided into control group and diabetes mellitus (DM) group. In the DM group, a rat model of type 1 DM was established with a single intraperitoneal injection of streptozotocin. After 8 weeks of induction for the DCM model, the obtained rats with DCM were randomly divided into DCM group, DCM+prostaglandin E1 (PGE1) group, DCM+low-molecular-weight heparin (LMWH) group, DCM+PSS group, and DCM+PSS-NP group. The treatment groups were intraperitoneally injected with PGE1 5 μg?kg-1?d-1, LMWH 150 U?kg-1?d-1, PSS 20 mg?kg-1?d-1, and PSS-NP 20 mg?kg-1?d-1, respectively, while the control group and DCM group were given intraperitoneal injection of an equal volume of normal saline. After four weeks of treatment, hematoxylin-eosin (HE) staining was used to observe the pathological changes of the thoracic aorta. ELISA was used to determine the concentration of protein C receptor (PROCR) in endothelial cells of the thoracic aorta. Western blot was used to determine the protein expression of phosphoinositide-3 kinase (PI3K)-p85 and vascular endothelial growth factor A (VEGFA) and the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and protein kinase-B (Akt) in the thoracic aorta.
Results HE staining showed that the thoracic aorta in the DCM group had irregular intima, endothelial cell destruction, and different sizes of cell nucleus, and the endothelial morphology of the thoracic aorta in DCM rats was significantly improved by PSS-NP. ELISA results showed that compared with the control group, the DCM group had a significantly reduced concentration of PROCR; compared with the DCM group, all treatment groups had a significantly increased concentration of PROCR, and the DCM+PSS-NP group had the greatest increase (F=16.03,P<0.01). The Western blot findings exhibited that compared with the control group, the DCM group had significantly reduced protein expression of PI3K-p85 and VEGFA and phosphorylation levels of Akt and eNOS; compared with the DCM group, all treatment groups had significantly increased protein expression of PI3K-p85 and VEGFA and phosphorylation levels of Akt and eNOS, and the DCM+PSS-NP group had the greatest increases (F=10.06-14.13,P<0.01).
Conclusion PSS-NP may improve STZ-induced endothelial injury of the thoracic aorta in DCM rats via up-regulating the PI3K/Akt/eNOS/VEGFA signaling pathway.
更新日期/Last Update: 2018-06-05