文章摘要
扈若凡,周 洁,梁声茹,鱼馨文,姬秋和.达格列净对高渗诱导的血管内皮细胞衰老的干预研究[J].,2020,(12):2219-2223
达格列净对高渗诱导的血管内皮细胞衰老的干预研究
Effects of Dapagliflozin on Hyperosmotic-induced Endothelia Vascular Cells Senescence
投稿时间:2020-01-26  修订日期:2020-02-28
DOI:10.13241/j.cnki.pmb.2020.12.004
中文关键词: 达格列净  高渗  血管内皮细胞  细胞衰老
英文关键词: Dapagliflozin  Hyperosmolarity  Human vascular endothelial cells  Cell senescence
基金项目:国家重点研发计划项目(2017YFC1309803)
作者单位E-mail
扈若凡 空军军医大学附属西京医院内分泌科 陕西 西安 710032 huruofan75@sina.com 
周 洁 空军军医大学附属西京医院内分泌科 陕西 西安 710032  
梁声茹 空军军医大学附属西京医院内分泌科 陕西 西安 710032  
鱼馨文 空军军医大学附属西京医院内分泌科 陕西 西安 710032  
姬秋和 空军军医大学附属西京医院内分泌科 陕西 西安 710032  
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中文摘要:
      摘要 目的:探讨SGLT2i类药物达格列净(dapagliflozin)对高渗诱导的人脐静脉内皮细胞(HUVECs)衰老的影响。方法:将 HUVECs 分为空白组(Blank组)、高渗330组(M-330组)、高渗350组(M-350组)、达格列净+高渗组(DAPA+M-350组),高渗培养环境由甘露醇诱导。衰老相关β-半乳糖苷酶(SA-β-Gal) 染色检测细胞衰老情况;免疫荧光染色检测SGLT2表达变化;Western blot检测SGLT2、细胞衰老标志物p21的表达变化,JC-1染色试剂盒检测线粒体膜电位的变化。结果:免疫荧光染色和western blot结果显示,Blank组,M-330组及M-350组细胞上均存在SGLT2受体蛋白表达,且Blank组,M-330组及M-350组的SGLT2表达依次显著增加。与Blank组相比,M-350组SA-β-Gal胞质蓝染、染色阳性率、衰老蛋白p21及SGLT2表达显著增加,并伴有线粒体膜电位的显著下降(P<0.05);DAPA+M-350组与M-350组相比,SA-β-Gal胞质蓝染、染色阳性率和p21表达显著下降,并伴有线粒体膜电位的显著上升(P<0.05)。结论:HUVECs上存在SGLT2受体蛋白,且在300-350 mOsm/L范围内随着渗透压的升高而增加,达格列净可改善高渗所诱导的血管内皮细胞衰老,其机制可能与达格列净改善高渗导致的线粒体功能障碍有关。
英文摘要:
      ABSTRACT Objective: To investigate the effects of dapagliflozin on the hyperosmolarity- induced vascular endothelial cells senescence. Methods: The human umbilical vascular endothelial cells (HUVECs) were divided into 4 groups: Blank group (Blank group), hypertonic-330 group (M-330 group), Hyperosmolarity -350 group (M-350 group), Dapagliflozin + Hyperosmolarity -350 group (DAPA+ M-350 group). Hyperosmolarity cells culture environment induced by mannitol. Senescence-associated β-galactosidase (SA-β-Gal) staining was performed to measure the senescent cells in Blank group, M-350 group and DAPA+ M-350 group. The protein levels of SGLT2 was detected by immunofluorescence staining and Western blot in Blank group, M-330 group and M-350 group. The mitochondrial membrane potential was detected by JC-1 staining kit and p21 was detected by Western blot in Blank group, M-350 group and DAPA+ M-350 group. Results: The results of immunofluorescence and Western blot showed that SGLT2 receptor protein expression was found in in Blank group, M-330 group and M-350 group, and the protein levels SGLT2 in the three groups increased markedly in turn. Additionally, compared with Blank group, the rates of positive cells and the degree of blue staining in cytoplasm of SA - β - gal staining , and the protein levels of p21 and SGLT2 in M-350 group increased significantly, with the mitochondrial membrane potential decreased significantly (P<0.05); Moreover, compared with M-350, the positive rates of SA - β - gal staining and the protein levels of p21 decreased significantly in DAPA+M-350 group, with the mitochondrial membrane potential increased markedly (P<0.05). Conclusion: SGLT2 receptor protein was found on HUVECs. The expression of SGLT2 receptor protein is up-regulated with the increase of osmotic pressure in the range of 300-350 mOsm/L. Dapagliflozin can reduce the senescence of vascular endothelial cells induced by hyperosmolarity, and its mechanism may be related to dapagliflozin can improve mitochondrial dysfunction.
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