期刊文献+

高糖诱导下人肾小球系膜细胞AMPK、MPO、α-SMA的变化以及α-硫辛酸的干预作用 被引量:5

High glucose-induced AMPK and MPO and α-SMA changes of human mesangial cells and the effect of α-lipoic acid
下载PDF
导出
摘要 目的探讨高糖诱导下人肾小球系膜细胞(HMCs)中腺苷酸活化蛋白激酶(AMPK)、炎症反应指标、细胞外基质的变化及α-硫辛酸的干预作用。方法传代培养的HMCs同步化后分组:正常对照组、高糖组、甘露醇对照组、高糖+α-硫辛酸处理组(α-硫辛酸浓度分别为50、100和200μmol/L),于实验0、12、24、48和72 h收集各组细胞及上清液,采用RT-PCR法和ELISA法检测各组细胞中AMPK mRNA及上清液中AMPK、髓过氧化物酶(MPO)、α-平滑肌肌动蛋白(α-SMA)的含量。结果高糖组人肾小球系膜细胞AMPK mRNA及AMPK蛋白的表达较正常对照组明显下降(P<0.01),MPO、α-SMA蛋白的表达明显增加(P<0.01)。α-硫辛酸各处理组AMPK mRNA及AMPK蛋白表达比高糖组有明显增加(P<0.01),MPO、α-SMA蛋白的分泌较处理前明显降低(P<0.05)。结论高糖能够抑制人肾小球系膜细胞中AMPK的表达,诱导MPO(炎症反应指标)、α-SMA(系膜细胞活化从而分泌细胞外基质增多的指标)的表达,抗氧化剂α-硫辛酸可以上调高糖抑制的AMPK的表达,减少高糖刺激下HMCs中MPO、α-SMA蛋白的分泌,为糖尿病肾病的防治提供新的理论依据。 [ Objective] To investigate the changes of AMPK and inflammation index and extracellular ma- trix in the process of human mesangial cells (HMCs) induced by high glucose and the effect of α--lipoic acid. [Methods] Synchronized HMCs were divided into following groups: normal control group (5.5 mmol/L G), High glucose group (30 mmol/L G), mannitol group (5.5 mmol/L G with 24.5 mmol/L mannitol), high glucose + α-lipoic acid groups (30 mmol/L G with α-lipoic acid 50 μmol/L, 100 μmol/L, 200 μmol/L). The supernatant and cells were collected at 0 h, 12 h, 24 h, 48 h and 72 h respectively, the concentration changes of the AMPK mRNA were determined by Real-time PCR method in the cells, then the ELISA method was used to check the protein expression of the MPO, α-SMA in the supernatant. [Results] AMPK mRNA and AMPK protein of the HMCs cultured under the high glucose expressed significantly lower than the ones of the HMCs in the normal group (P〈0.01), and the MPO, α-SMA protein secretion was increased (P〈0.01). After the α- lipoic acid pretreatment, compared with without treatment groups, AMPK mRNA expression and AMPK proteinsecretion were significantly increased (P〈0.01), the MPO, α-SMA protein secretion was significantly reduced compared with that before (P 〈0.05). [ Conclusion] High glucose can inhibit the expression of AMPK in HM- Cs, up-regulate the expression of MPO, α--SMA. A-lipoic acid can stimulate the expression of AMPK protein and reduce the expression of MPO,α-SMA induced by high glucose in HMCs, supporting a potential role in treatment of diabetic kidney disease.
出处 《中国现代医学杂志》 CAS CSCD 北大核心 2013年第8期17-21,共5页 China Journal of Modern Medicine
基金 辽宁省科技攻关计划资助项目(No:2011225017) 沈阳市科技攻关计划项目(No:F11-262-9-06)
关键词 腺苷酸活化蛋白激酶 人肾小球系膜细胞 炎症反应 细胞外基质 Α-硫辛酸 AMP-activated protein kinase human mesangial cells inflammatory response extracellularmatrix α-lipoic acid
  • 相关文献

参考文献19

  • 1DHAUNSI GS, BITAR MS. Antioxidants attenuate diabetes-induced activation of peroxisomal functions in the rat kidney[J]. J Biomed Sci, 2004, 11(5): 566-570.
  • 2ARAUJO M, WELCH WJ. Oxidative stress and nitric oxide in kidney function[J]. Curr Opin Ncphrol Hypertens, 2006, 15(1): 72-77.
  • 3FUJII H, KONO K, NAKAI K, et al. Oxidative and nitrosative stress and progression of diabetic nephropathy in type 2 diabetes [J]. Am J Nephrol, 2010, 31(4): 342-352.
  • 4XIAO H, LI Y, QI J, et al. Peroxynitrite plays a key role in glomerular lesions in diabetic rats[J]. J Nephrol, 2009, 22 (6): 800-808.
  • 5VLASSARA H, TORREGGIANI M, POST JB, et al. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging[J]. Kidney Int Suppl, 2009, (114): 3-11.
  • 6WU J, MEI C, VLASSARA H, et al. Oxidative stress-induced JNK activation contributes to proinflammatory phenotype of aging diabetic mesangial cells[J]. Am J Physiol Renal Physiol, 2009, 297(6): 1622-1631.
  • 7LEE MJ, FELIERS D, MARIAPPAN MM, et al. A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy[J]. Am J Physiol Renal Physiol, 2007, 292(2): 617-627.
  • 8EID AA, FORD BM, BLOCK K, et al. AMP-activated protein kinase (AMPK) negatively regulates Nox4 dependent activation of p53 and epithelial cell apoptosis in diabetes[J]. J Biol Chem, 2010, 285(48): 37503-37512.
  • 9SU YX, DENG HC, ZHANG MX, et al. Adiponectin inhibits PDGF-induced mesangial cell proliferation: regulation of mammalian target of rapamycin mediated survival pathway by adenosine 5-monophosphate activated protein kinase[J]. Horm Metab Res, 2012, 44(1): 21-27.
  • 10ZHUO L, FU B, BAI X, et al. NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtu- ins-AMPK-mTOR pathway[J]. Cell Physiol Biochem, 2011, 27 (6): 681-690.

同被引文献61

引证文献5

二级引证文献27

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部