| 王丽娜,胡松,颜贵英,等.藻酸双酯钠纳米剂型对糖尿病心肌病大鼠冠脉微循环血栓调节蛋白表达的影响△[J].中国海洋药物,2018,37(5):60-66. |
| 藻酸双酯钠纳米剂型对糖尿病心肌病大鼠冠脉微循环血栓调节蛋白表达的影响△ |
| Effect of propylene glycol alginate sodium sulfate nanoparticleson the expression of thrombomodulin in coronary microcirculation of Diabetic cardiomyopathy rats |
| 投稿时间：2014-12-23 修订日期：2015-12-29 |
| DOI： |
| 中文关键词: 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 |
| English Keywords:propylene glycol alginate sodium nanoparticles diabetic cardiomyopathy coronary microcirculation thrombomodulin |
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| 中文摘要: |
| 目的：探讨藻酸双酯钠纳米剂型(PSS-NP)对链脲佐菌素(STZ)诱导的糖尿病心肌病（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,其余12只为正常对照组。诱导后8周，采用心脏超声检测大鼠心功能变化筛选DCM大鼠,DCM大鼠随机分为空白组、溶媒组、阳性对照组、藻酸双酯钠组、藻酸双酯钠纳米剂型组，并分别给予生理盐水及相应药物灌胃6周。于诱导后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，体重明显减轻（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水平明显升高（P＜0.05），其中空白组、溶媒组水平最高（两者无显著性差异，P＜0.05）,其次为PSS组，PSS-NP组、阳性对照组水平最低（两者无显著性差异，P＜0.05）；TM-mRNA表达水平明显升高（P＜0.05）,其中空白组、溶媒组水平最高（两者无显著性差异，P＜0.05），其次为PSS组,德纳组、PSS-NP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。 |
| English Summary: |
| Objective: To investigate the effect of propylene glycolalginate sodiumsulfate nanoparticles(PSS-NP) on the expression of thrombomodulin in streptozotocin (STZ) induced diabetic cardiomyopathy ratssand its possible mechanism. Methods:40 rats were selected randomly from 52 male wistar rats as the model group and the remaining 12 asthe control group.Dabetes 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 control group, propylene glycol alginatesodium（PSS）group, propylene glycol alginate sodium 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 ratsare 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%, EA ratio were significantly decreased (P <0.05),and LVEDs, 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: Amongall 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.Conclusions: Compared with traditional formulations, propylene glycol alginate sodium sulfate nanoparticles can inhibit the expression of TM in DCM rats.Thus it is valuable for the treatment of DCM microcirculation dysfuctions.
Keywords: propylene glycol alginate sodium; nanoparticles; diabetic cardiomyopathy; coronary microcirculation; thrombomodulin |
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