期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

PPARγ激动剂罗格列酮在大鼠肝缺血再灌注损伤中的作用及机制探讨 被引量：7

Effect of peroxisome proliferator-activated receptor γ activator rosiglitazone in rat hepatic ischemia-reperfusion injury and its mechanism
下载PDF
导出
摘要 目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮在大鼠肝脏缺血再灌注损伤中的作用及机制。方法:建立70%的大鼠肝脏缺血再灌注损伤模型,SD大鼠随机分为6组,对照组(control,C),假手术组(sham,S),缺血再灌注损伤(ischemia-reperfusion,IR)组,罗格列酮(rosiglitazone,Ros)预处理组,GW9662预处理组,以及Ros+GW9662预处理组。再灌注后,取静脉血检测肝血清酶(ALT、AST)水平,取肝脏组织TUNEL法检测缺血肝脏细胞凋亡指数(apoptotic index,AI),免疫组化检测Bcl-2,Bax,Caspase-3表达。结果:IR组和Ros组与假手术组相比肝脏细胞凋亡指数、Bax、Bcl-2及Caspase-3均升高。Ros处理组与IR组相比肝脏细胞凋亡指数、Bax及Caspase-3表达降低,Bcl-2表达升高,GW9662能阻断Ros的保护作用。单独应用GW9662时肝脏细胞凋亡指数、Caspase-3以及Bax表达比IR组升高,而Bcl-2降低。结论:PPARγ激动剂罗格列酮对肝脏缺血再灌注损伤有保护作用,它可能是通过上调Bcl-2表达,下调Bax和Caspase-3表达,抑制肝脏细胞凋亡而起作用的。 Objective：To investigate the effect of peroxisome proliferator-activated receptor γ（PPARγ） activator rosiglitazone in rat hepatic ischemia-reperfusion injury and its mechanism. Methods：The model of 70% warm ischemia-reperfusion injury was established in SD rats. Rats were divided randomly into 6 groups：control group, sham group, ischemia-reperfusion group, rosiglitazone group ,2-chloro-5-nitrobenzanilide （GW9662） treatment group and rosiglitazone plus GW9662 treatment group. After reperfusion, AST and ALT levels in serum were detected. The liver tissue was removed for t of the apoptotic index by TUNEL assay, and the expression of Bax, Bcl-2 and caspase-3 proteins in ischemic hepatocytes were detected by immunohistochemistry. Results： Compared with sham group, the apoptotic index of hepatocytes, expressions of Bax, Bcl-2 and Caspase-3 proteins in ischemia- reperfusion group and rosiglitazone group was greatly increased. Compared with ischemia-reperfusion group, the apoptosis index of hepatocytes, expressions of Bax and Caspase-3 in rosiglitazone group decreased, with Bcl-2 increased. GW9662 abolished the protective effect of rosiglitazone. GW9662 treated alone increased the apoptosis index of hepatocytes, Bax and Caspase-3, with the expression of Bcl-2 decreased. Conclusion：PPARγ activator rosiglitazone could protect against ischemia-reperfusion injury in rats, with its possible mechanism of upregulating the expression Of Bcl-2, inhibiting the expression of Bax and Caspase-3, and prohibiting hepatocyte apoptosis.
作者 曹晓飞 张峰 张业伟
机构地区 南京医科大学第一附属医院肝脏移植中心
出处 《南京医科大学学报（自然科学版）》 CAS CSCD 北大核心 2007年第11期1271-1273,1289,共4页 Journal of Nanjing Medical University(Natural Sciences)
关键词 过氧化物酶体增殖物激活受体Γ 再灌注损伤 罗格列酮 凋亡 peroxisome prpliferator-activated receptor γ reperfusion injury msiglitazone apoptosis
分类号 R657.3 [医药卫生—外科学]
  • 相关文献

参考文献12

  • 1Evans EM.The steroid and thyroid hormone receptor superfamily[J].Science,1988,240:889-895
  • 2Ohmori M,Miyashita F,Uchida H,et al.Effect of erythromycin on ischemia-reperfusion injury of liver in rats[J].Transplant Proc,2000,32 (4):811-814
  • 3Busuttil R.Liver ischaemia and reperfusion injury[J].Br J Surg,2007,94(7):787-788
  • 4Jaeschke H.Molecular mechanisms of hepatic ischemiareperfusion injury and precondi-tioning[J].Am J Physiol Gastrointest Liver Physiol,2003,284:G 15-G26
  • 5Collino M,Aragno M,Mastrocola R,et al.Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion[J].Eur J Pharmacol,2006,530(1-2):70-80
  • 6Cuzzocrea S,Pisano B,Dugo L,et al.Rosiglitazone,a ligand of the peroxisome proliferator-activated receptorgamma,reduces the development of nonseptic shock induced by zymosan in mice[J].Crit Care Med,2004,32:457-466
  • 7Zingarelli B,Sheehan M,Hake PW,et al.Peroxisome proliferator activator receptor-gamma ligands,15-deoxydelta (12,14)-prostaglandin J2 and ciglitazone,reduce systemic inflammation in polymicrobial sepsis by modulation of signal transduction pathways[J].J Immunol,2003,171:6827-6837
  • 8Malhi H,Gores GJ,Lemasters JJ.Apoptosis and necrosis in the liver:a tale of two deaths[J]? Hepatology,2006,43:S31-44
  • 9Green DR,Reed JC.Mitochondria and apoptosis[J].Science,1998,281:1309-1312
  • 10Amstad PA,Liu H,Ichimiya M,et al.Bcl-2 is involved in preventingoxidant-induced cell death and in decreasing oxygen radical production[J].Recox Rep,2001,6:351-362

二级参考文献15

  • 1杨俊,计振民,何畏,周晨,张鹏翎,王昆,刘超.辛伐他汀对糖尿病肾病患者UALB及TGFβ_1、IV型胶原和层黏连蛋白的影响[J].南京医科大学学报（自然科学版）,2006,26(7):582-584. 被引量：4
  • 2Kohzuki M,Wu XM,Kamimoto M,et al.Renal protective effect of nondepressor dose of cicletanine in streptozotocin diabetic rats[J].J Hypertens,1999,17(5):695-700
  • 3Adlers.Structure-function relationships in diabetic nephropathy:lesions and limitation[J].Kidney Int,1997,52:S42-S45
  • 4Nazarenko IA,Bhatnagar SK,Hohman RJ.A closed tube format for amplification and detection of DNA based on energy transfer[J].Nucleic Acids Res,2003,25 (12):2516-2521
  • 5Sugiyama H,Kashihara N,Makino H,et al.Apoptosis in glomerular sclerosis[J].Kidney Int,1996,49:103-111
  • 6Rayner B.Advances in the treatment of diabetic renal disease:focus on losartan[J].Curr Med Res Opin,2004,20(3):333-340
  • 7Dinender Kumar,Joseph Zimpelmann,Susan Robertson,et al.Tubular and interstitial cell apoptosis in the streptozotocin-diabetic rat kidney[J].Nephron Exp Nephrol,2004,96:e77-e88
  • 8Qin J,Zhang Z,Liu J,et al.Effects of the combination of an angiotensin Ⅱ antagonist with an HMG-CoA reductase inhibitor in experimental diabetes[J].Kidney Int,2003,64(2):565-571
  • 9Blanco-C LM,Villa A,Ortego M,et al.3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors,atorvastatin and simvastatin,induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation[J].Atherosclerosis,2002,161 (1):17-26
  • 10Blanco-Colio LM,Justo P,Daehn I,et al.Bcl-xL overexpression protects from apoptosis induced by HMG-CoAreductase inhibitors in murine tubular cells[J].Kidney Int,2003,64(1):181-191

共引文献1

同被引文献24

  • 1Hoet PH,Lewis CP,Demedts M,et al.Putrescine and paraquat uptake in human lung slices and isolated type II pneumocytes[J].Biochem Pharmacol,1994,48(3):517-524.
  • 2Walsh JG,Cullen SP,Sheridan C,et al.Executioner caspase-3and caspase-7 are functionally distinct proteases[J].Proc Natl Acad Sci U S A,2008,105(35):12815-9.
  • 3Matsumoto T,Noguchi E,Kobayashi T,et al.Mechanisms underling the chronic pioglitazone treatment-induced improvement in the impaired endothelium-dependent relaxation seen in aortas from diabetic rats[J].Free Radic Biol M ed,2007,42(7):993-1007.
  • 4Wang WM,Chen H,Zhong F,et al.Inhibitory effects of rosiglitazone on lipopolysaccharide-induced inflammation in a murine model and HK-2 cells[J].Am J Nephrol,2011,34(2):152-162.
  • 5Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits[J].Anesth Analg,2003,97(6):1751-1755.
  • 6Meade AJ,Meloni BP,Cross J,et al.AP-1 inhibitory peptides are neuroprotective follow ing acute glutamate excitotoxicity in primary cortical neuronal cultures[J].J Neurochem,2010,112(1):258-270.
  • 7Caramori G,Ito K,Adcock IM.Transcription factors in asthma and COPD[J].IDrugs,2004,7(8):764-770.
  • 8Dinis-Oliveira RJ,Sousa C,Remiao F,et al.Sodium salicylate prevents paraquat-induced apoptosis in the rat lung[J].Free Radic Biol M ed,2007,43(1):48-61.
  • 9Belvisi MG,Hele DJ,Birrell MA.Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airw ay inflammation[J].Eur J pharmacol,2006,533(1-3):101-109.
  • 10David BB,Jessica W.Peroxisome proliferator-activated receptors:a critical review on endogenous pathw ays for ligand generation[J].Prostaglandins Other Lipid M ediat,2003,71(1-2):1-22.

引证文献7

二级引证文献20

南京医科大学学报（自然科学版）
2007年 第11期

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