内科论文

您当前的位置:学术堂 > 医学论文 > 临床医学论文 > 内科论文 >

胰高血糖素样肽素-1对糖尿病患者心肌细胞的保护功能(4)

来源:中国药理学通报 作者:张军,谷翔,黄问银,张
发布于:2017-06-19 共7621字
  本研究首先检测了Bax和Bcl-2的表达变化,研究表明 GLP-1 对细胞凋亡的抑制是否与 Bcl-2 的上调和 Bax 的下调有关。Western blot 实验表明,与正常组相比,AGEs 组的促凋亡蛋白 Bax 表达量明显增加,而抑制凋亡蛋白 Bcl-2 的表达量减少; 而与AGEs 组相比,AGEs + GLP-1 组下调促凋亡蛋白 Bax表达,上调抑制凋亡蛋白 Bcl-2 的表达。本研究结果说明,GLP-1 可能通过调控 Bax 和 Bcl-2 蛋白的表达而缓解氧化损伤。
  
  【Fig 5 Effect of GLP-1on AGEs-inducedapoptosis of H9C2( x珋 ± s,n = 4)##P < 0. 01 vs control;*P < 0. 05 vs AGEs】  
  流式细胞术检测结果显示,GLP-1 作用后,AGEs 所导致的 H9C2 细胞凋亡率减少; AGEs 损伤组细胞 DCFH-DA 荧光强度水平升高,DCFH-DA 是活性氧的指示剂,细胞氧化应激时,ROS 产生增加;GLP-1 处理使 DCF-DA 荧光强度水平降低,说明GLP-1 可以清除活性氧,减轻心肌脂质过氧化,对抗AGEs 引起的氧化应激,减轻细胞损伤。结果说明GLP-1 可能通过调控细胞氧化还原系统,减少AGEs 引起的 ROS 过量堆积,进而保护心肌细胞。
  
  【Fig 6 Effect of GLP-1 on anti-apoptoticBcl-2 and pro-apoptotic Bax expression( x珋 ± s,n = 4)B、C: Show that the protein expression of each group H9C2 was de-termined by Western blot.#P < 0. 05,##P < 0. 01 vs control;*P < 0. 05,**P < 0. 01 vs AGEs group】  
  综上所述,GLP-1 拮抗 AGEs 诱导心肌细胞氧化损伤所导致的凋亡作用,且能通过调控凋亡相关蛋白发挥对心肌细胞保护作用。上述实验结果对GLP-1 抗氧化研究、防治糖尿病心血管并发症等疾病具有重要意义。
  
  参考文献:
  
  [1] Prasad A,Bekker P,Tsimikas S. Advanced glycation end productsand diabetic cardiovascar disease[J]. Cardiol Rev,2012,20( 4) :177 - 83.  
  [2] Ramasamy R,Yan S F,Schmidt A M. Receptor for AGE( RAGE) : signaling mechanisms in the pathogenesis of diabetesand its complications[J]. Ann New York Acad Sci,2011,1243:88 - 102.  
  [3] van den Oever IA,Raterman H G,Nurmohamed M T,et al . Endo-thelial dys-function,inflammation and apoptosis in diabetes melli-tus[J]. Mediators Inflamm,2010,2010: 792393.  
  [4] Santos C X,Anilkumar N,Zhang M,et al. Redox signaling in car-diacmyocytes [J]. Free Radic Biol Med,2011,50( 7) : 777 - 93.  
  [5] Kajstura J,Cheng W,Reiss K,et al. Apoptotic and necrotic myo-cyte cell deaths are independent contributing variables of infarctsize in rats[J]. Lab Invest,1996,74( 1) : 86 - 107. 
  [6] Rodrigo R,Libuy M,Feliu F,et al. Molecular basis of cardiopro-tective effect of antioxidant vitamins in myocardial infarction[J].Biomed Res Int,2013,2013: 437613.  
  [7] Ishibashi Y,Matsui T,Takeuchi M,Yamagishi S. Glucagon-likepeptide-1 ( GLP-1 ) inhibits advanced glycation end product( AGE) -induced up-regulation of VCAM-1 mRNA levels in endo-theial cells by suppressing AGE receptor ( RAGE) expression[J].Biochem Biophysical Res Communications,2010,391( 3) : 1405 -8.  
  [8] Ishibashi Y,Matsui T,Takeuchi M,Yamagishi S. Sitagliptin aug-ments protective effects of GLP-1 against advanced glycation endproduct receptor axis in endothelial cells[J]. Horm Metab Res,2011,43( 10) : 731 - 4.  
  [9] Zhao X,Liu G,Shen H,Gao B,et al. Liraglutide inhibits auto-phagy and apoptosis induced by high glucose through GLP-1R inrenal tubular epithelial cells[J]. Int J Mol Med,2015,35 ( 3 ) :684 - 92.  
  [10] Lonborg J,Vejlstrup N,Kelbaek H,et al. Impact of acute hyper-glycemia onmyocardial infarct size,area at risk,and salvage in pa-tients with STEMI and the association with exenatide treatment: re-sults from a randomized study[J]. Diabetes,2014,63( 7) 2474 -85.  
  [11] 胡 波,李德才。 糖基化终产物对心肌细胞 GLP-1 受体表达及凋亡影响的研究[J]. 四川医学,2013,34( 6) : 746 -8.  
  [11] Hu B,Li D C. Effects of advanced glycation end-products on theexpression of GLP-1 receptor and apopotis in cultured cardiomyo-cytes[J]. Sichuan Med J,,2013,34( 6) : 746 - 8.  
  [12] 曾 平,许顶立,李 针,等。 晚期糖基化终产物对心肌细胞细胞周期和凋亡的影响[J]. 第一军医大学学报,2003,23( 1) : 9- 11.  
  [12] Zeng P,Xu D L,Li Z,et al. Eeffect of advanced glycation end-products on cell cycle distribution and apoptosis in neonatal ratcardiac myocytes[J]. J First Mil Med Univ,2003,23 ( 1 ) : 9 -11.  
  [13] Hegab Z,Gibbons S,Neyses L,et al. Role of advanced glycationend products in cardiovascular disease[J]. World J Cardiol,2012,26( 4) : 90 - 102.  
  [14] Diguet N,Mallat Y,Ladouce R,et al. Muscle creatine kinase defi-cien-cy triggers both actin depolymerization and desmindisorganiza-tion by advanced glycation end products in dilated cardiomyopathy[J]. J Biological Chem,2011,286( 40) : 35007 -19.  
  [15] Budak L,Labuzek K,Budak R J,et al,Exenatide ( a GLP-1 ago-nist) improves the antioxidative potential of in vitro cultured hu-man monocytes / macrophages[J]. Naunyn Schmiedebergs ArchPharmacol,2015,388( 9) : 905 - 19. 
  [16] Zhu T,Wu X L,Zhang W,Xiao M. Glucagon like peptide-1( GLP-1) modulates OVA-induced airway inflammation and mucussecretion involving a protein kinase A ( PKA) -dependent nuclearfactor-κB ( NF-κB) signaling pathway in mice[J]. Int J Mol Sci,2015,16( 9) : 20195 - 211. 
  [17] Ueda Y,Hirai S I,Osada S I,et al. Protein kinase C delta acti-vates the MEK-ERK pathway in a manner independent of Ras anddependent on Raf[J]. J Biol Chem,1996,271( 38) : 23512 - 9.  
  [18] Zhang Q,Huang W D,Lü X Y,et al. Puerarin protects differen-tiated PC12 cells from H2O 2 -induced apoptosis through thePI3K / Akt signalling pathway[J]. Cell Biol Int,2012,36: 419 -26.  
  [19] 牛子冉,徐晓娜,陈俞材,等。 丹酚酸 A 对异丙肾上腺素致小鼠心肌缺血的保护作用及其机制[J]. 中国药理学通报,2015,31( 12) : 1667 - 74.  
  [19] Niu Z R ,Xu X N,Chen Y C,et al. Protective effect of Salvianolicacid A against isoproterenol-induced myocardial infarction in mice[J]. Chin Pharmacol Bull,2015,31( 12) : 1667 -74.  
  [20] Adams J M,Cory S. The Bcl-2 protein family: arbiters of cell sur-vival[J] Sci,1998,281( 5381) : 1322 - 6.  
  [21] 谢荣辉,殷明,殷嫦嫦,等。 N-乙酰半胱氨酸对过氧化氢诱导的骨髓间充质干细胞凋亡的保护及作用机制研究[J]. 中国药理学通报,2014,30( 1) : 54 -9.  
  [21] Xie R H,Yin M,Yin C C et al,Effect of N-Acetyl-L-cysteine onprotection research in H2O2-Induced mesenchymal stem cells ap-optosis[J]. Chin Pharmacol Bull,2014,30( 1) : 54 - 9.  
  [22] Cheng E H,Wei M C,Weiler S,et al. BCL-2,BCL-X( L) sequesterBH3 domain-only molecules preventing BAX-and BAK-mediatedmitochondrial apoptosis[J]. Mol Cell,2001,8( 3) : 705 - 711.
作者单位:
原文出处:张军,谷翔,黄问银,张普华,殷嫦嫦,于欢,张义平,王丽丽,李卫东. GLP-1对AGEs诱导H9C2心肌细胞凋亡的保护作用研究[J]. 中国药理学通报,2017,(01):120-126.
相关内容推荐
相关标签:
返回:内科论文