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  • 曾盈,杨克,吕立夏,等.胰高血糖素样多肽1抑制高糖诱导的高迁移率组蛋白B1表达及机制研究[J].同济大学学报(医学版),2015,36(6):8-12, 18.    [点击复制]
  • ZENG Ying,YANG Ke,LV Li-xia,et al.Effects of glucagon like peptide 1 on high glucose induced expression of high mobility group box-1 protein in human retinal capillary endothelial cells and its mechanism[J].同济大学学报(医学版),2015,36(6):8-12, 18.   [点击复制]
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胰高血糖素样多肽1抑制高糖诱导的高迁移率组蛋白B1表达及机制研究
曾盈,杨克,吕立夏,徐国彤
0
(同济大学医学院再生医学系,上海 200092;上海交通大学医学院附属瑞金医院心血管病研究所,上海 200025)
摘要:
目的 研究胰高血糖素样多肽1(glucagon like peptide 1, GLP-1)对高糖环境下培养的人视网膜微血管内皮细胞(human retinal capillary endothelial cells, HRCEC)中,高迁移率组蛋白B1(high mobility group box-1 protein, HMGB1)表达的影响及相关机制。方法 高糖刺激HRCEC不同时间(24h、48h及96h)后,分别使用不同浓度的GLP-1(10mmol/L、100nmol/L及1000nmol/L)刺激HRCEC 96h后,分别通过RT-PCR、ELISA及Western Blot检测HMGB1的mRNA、分泌及蛋白水平。使用高糖和GLP-1刺激细胞1h后,Western Blot检测HMGB1表达相关信号通路(p38 MAPK、JNK和NF-κB)磷酸化水平。结果 相较于正常糖水平,高糖促使HMGB1的mRNA、分泌及蛋白水平显著升高,GLP-1可有效抑制这一效应。高糖可显著性激活p38 MAPK、JNK和NF-κB,而GLP-1则抑制高糖所诱导的这些信号通路激活。结论 GLP-1可能通过抑制高糖刺激下HMGB1的表达及炎症信号通路激活,从而抑制糖尿病视网膜病变的发生及发展。
关键词:  胰高血糖素样多肽1  微血管内皮细胞  高迁移率组蛋白B1
DOI:10.16118/j.1008-0392.2015.06.002
投稿时间:2015-08-09
基金项目:国家自然科学基金(31171419)
Effects of glucagon like peptide 1 on high glucose induced expression of high mobility group box-1 protein in human retinal capillary endothelial cells and its mechanism
ZENG Ying,YANG Ke,LV Li-xia,XU Guo-tong
(Dept.of Regenerative Medicine, Medical College, Tongji University, Shanghai 200092, China;Institute of Cardiovascular Research, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China)
Abstract:
Objective To investigate the effects and related mechanisms of glucagon like peptide 1(GLP-1) on mRNA and protein expression of high mobility group box-1 protein(HMGB1) in human retinal capillary endothelial cell(HRCEC) induced by high glucose. Methods Human retinal capillary endothelial cells(HRCECs) were treated with GLP-1 in different doses(10nmol/L,100nmol/L,1000nmol/L) for 24h, 48h and 96h, the expression of HMGB1 mRNA and protein was detected with RT-PCR and Western Blot, respectively. HMGB1 contents in culture medium were measured by ELISA. Phosphorylation level of p38 MAPK, JNK, and NF-κB was also measured by Western Blot. Results Compared with normal glucose culture, mRNA and protein expression level, and release of HMGB1 were significantly increased in HRCECs with high glucose culture, which was attenuated by treatment with GLP-1 in a dose-dependent manner. GLP-1 inhibited phosphorylation level of p38 MAPK, JNK, and NF-κB. Conclusion GLP-1 might attenuate the inflammation through inhibiting over-expression of HMGB1 in high glucose condition, which might prevent the diabetic retinopathy.
Key words:  glucagon like peptide 1  capillary endothelial cell  high mobility group box-1 protein

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