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目的:本研究旨在探讨人核心聚糖蛋白decorin是否可以缓解糖尿病心肌病并对其中机制进行探索。方法:在本研究中,采用Wistar大鼠作为研究对象,通过腹腔注射链唑霉素并采用高脂饮食喂养6个月诱导糖尿病心肌病模型。通过重组腺相关病毒介导大鼠心脏高表达decorin。在体外研究中,通过高浓度葡萄糖模拟在体高血糖刺激,并在人脐静脉内皮细胞中高表达decorin,通过研究细胞凋亡水平、成管能力、迁移能力和增殖能力,观察其对内皮细胞的保护效应。结果:结果显示,糖尿病心肌病大鼠表现为毛细血管密度减低、心肌纤维化以及心脏功能受损,而过表达decorin可以促进血管内皮生长因子(VEGF)的表达,增加血管密度,减轻心肌纤维化并缓解糖尿病心肌病大鼠的心脏功能。同时,体外研究结果也表明,高糖可以抑制IGF1R/AKT通路,抑制VEGF的表达,诱导内皮细胞的凋亡增加,抑制细胞的成管能力、迁移能力和增殖能力,而过表达decorin则缓解了上述效应。另外,抗IGF1R抗体预处理或者AKT抑制剂处理可以阻断decorin的保护作用。结论:Decorin可以通过激活IGF1R/AKT通路,上调VEGF的表达并促进血管生成,从而缓解糖尿病心肌病。
Aims: The purpose of this study was to investigate whether human decorin can relieve diabetic cardiomyopathy and to explore its mechanism. METHODS: In this study, Wistar rats were used as study subjects and diabetic cardiomyopathy models were induced by intraperitoneal injection of streptozotocin and high-fat diet for 6 months. Induction of high expression of decorin in rat heart by recombinant adeno - associated virus. In vitro studies showed that decorin was highly expressed in human umbilical vein endothelial cells by high glucose concentration and high expression of decorin, and its protective effect on endothelial cells was observed by studying apoptosis, tube formation, migration and proliferation effect. Results: The results showed that diabetic cardiomyopathy rats showed decreased capillary density, myocardial fibrosis and impaired cardiac function, whereas over-expression of decorin could promote the expression of vascular endothelial growth factor (VEGF), increase vascular density and reduce myocardial fibrosis And relieve cardiac function in diabetic cardiomyopathy rats. In addition, in vitro studies also showed that high glucose could inhibit the IGF1R / AKT pathway, inhibit the expression of VEGF, induce apoptosis of endothelial cells, inhibit the ability of cell formation, migration and proliferation, while over-expression of decorin alleviated The above effect. In addition, anti-IGF1R antibody pretreatment or AKT inhibitor treatment blocked the protective effect of decorin. Conclusion: Decorin can relieve diabetic cardiomyopathy by activating IGF1R / AKT pathway, up-regulating the expression of VEGF and promoting angiogenesis.