普罗布考对糖尿病肾病大鼠肾组织转化生长因子-1及血红素加氧酶-1表达的影响
Effect of probucol on the expression of transforming growth factor-1 and hemeoxygenase-1 in the renal tissue of diabetic nephropathy rats
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摘要: 目的:观察普罗布考(PB)对糖尿病肾病(DN)大鼠肾组织转化生长因子-1(TGF-1)及血红素加氧酶-1(HO-1)表达的影响,探讨PB延缓肾间质纤维化的机制。方法:50只雄性SD大鼠随机分为实验组及对照组。实验组行高糖高脂饮食,并以链脲佐菌素腹腔注射建立DN大鼠模型,将造模成功的大鼠随机分为DN组和PB组。PB组经口灌胃PB 500 mgkg-1d-1。实验结束称大鼠体质量并查24 h尿蛋白定量及尿N-乙酰--D-氨基葡萄糖苷酶(NAG);处死大鼠抽取血液,观察血清生化指标,摘除肾脏行组织切片,观察肾间质纤维化程度,免疫组织化学学检测肾组织内HO-1、TGF-1的表达,rT-PCr检测肾组织内TGF-1、HO-1核酸表达。结果:PB能减轻DN大鼠蛋白尿,降低尿NAG水平,改善血清总胆固醇;降低血清肌酐、尿素氮水平。上调肾组织HO-1mrNA水平,下调TGF-1mrNA水平。结论:PB可延缓肾组织纤维化,其机制可能与PB考上调HO-1的表达,进而下调TGF-1的表达相关。Abstract: Objective: To observe the effect of probucol(PB) on the expression of transforming growth factor-1 and hemeoxygenase-1 (HO-1) in the renal tissue of diabetic nephropathy (DN) rats，and investigate the mechanism of PB in delaying renal interstitial fibrosis. Methods: Fifty male Sprague-Dawlay(SD) rats were randomly divided into experimental group and control group. The rats in the experimental group were given high-sugar，high-fat diet and intraperitoneal injection of streptozotocin to establish DN rat models, the model rats were then randomly divided into DN group and PB group. The rats in the PB group were treated by oral gavage of PB 500 mgkg-1d-1 . At the end of the experiment, the rats were weighed and the 24 h urinary protein and urinary N-acetyl--Dglucosaminidase(NAG) were checked, the rats were killed to collect the blood; and the serum biochemical parameters were observed, the kidney of the model rats was removed and performed tissue section to observe the renal interstitial fibrosis, the expression of renal tissue HO-1 and TGF-1 was detected by immunohistochemistry，the nucleic acid expression of the renal tissue TGF-1 and HO-1 was detected by rT-PCr. results: PB could relieve the proteinuria in the rats with DN，degrade the urinary NAG level, improve the serum total cholesterol, and reduce the serum creatinine and blood urea nitrogen level. It could also upgrade the level of HO-1mrNA kidney tissue and downgrade the level of TGF-1mrNA. Conclusions: PB can delay renal fibrosis, the mechanism of which may be that PB could up-regulate the expression of HO-1 and down-regulate the expression of TGF-1 .
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Key words:
- diabetic nephropathy /
- probucol /
- renal interstitiadl fibrosis /
- hemeoxygenase-1 /
- transforming growth factor-1 /
- rat
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[2] Endo K，Miyashita Y，Sasaki H, et al. Probucol delays progression of diabetic nephropathy[J]. Diabetes res Clin Pract，2006，71 (2): 156-163. [2] Da ros r，Assaloni r，Ceriello A. Molecular targets of diabetic vascular complications and potential new drugs[J]. Curr Drug Targets, 2005，6 (4): 503-509. [3] Jarmi T，Agarwal A. Heme oxygenase and renal disease[J]. Curr Hypertens rep，2009, 11(1): 56-62. [4] Midwinter rG，Maghzal GJ，Dennis JM，et al. Succinobucol induces apoptosis in vascular smooth muscle cells[J]. Free radic Biol Med，2012，5 2(5): 871-879. [5] Wu BJ，Kathir K，Witting PK，et al. Antioxidants protect from atherosclerosis by a Heme oxygenase-1 pathway that is independent of free radical scavenging[J]. J Exp Med，2006，2 03 (4): 1117-1127. [6] 赵水平，王星，洪绍彩，等. 普罗布考对动脉粥样硬化兔血红素 氧合酶-1 表达的影响[J]. 中国动脉硬化杂志，2008，1 6(6): 440-444. [7] Zariou A，Aqarwal A. Heme oxygenase-1 as a target for TGF- in kidney disease[J]. Semin Nephrol, 2012, 32(3): 277-286. [8] 曾彩虹. 糖尿病肾病肾活检的临床意义及指征[J]. 肾脏病与 透析肾移植杂志，2 011，2 0(4): 346-347. [9] 徐鹏杰，李航，徐亚兰，等. 2 型糖尿病并发慢性肾脏病临床病 理特点分析[J]. 中华肾脏病杂志，2 010, 26(10): 731-735. [10] Palmeira CM，rolo AP，Berthiaume J，et al. Hyperglycemia decreases mitochondrial function: the regulatory role of mitochondrial biogenesis[J]. Toxicol Appl Pharmacol，2007，225 (2): 214-220. [11] Greiber S，Muller B，Daemisch P，et al. reactive oxygen species alter gene expression in podocytes: induction of granulocyte macrophage-colony-stimulating factor[J]. J Am Soc Nephrol, 2002, 13(1): 86-92. [12] Deng YM，Wu BJ，Witting PK，et al. Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1 [J]. Circulation，2004, 110(13): 1855-1860. [13] Traylor A，Hock T，Hill-Kapturczak N. Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-beta1 in renal epithelial cells[J]. Am J Physiol renal Physiol, 2007，2 93(3): F885-F894. [14] Samarakoon r，Overstreet JM，Higgins SP, et al. TGF-1SMAD/ p53/USF2 PAI-1 transcriptional in ureteral obstruction-induced renal fibrosis[J]. Cell Tissue res，2012，3 47(1): 117-128. [15] Hill-Kapturczak N，Truong L，Thamilselvan V，et al. Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor- in human renal epithelial cells[J]. J Biol Chem，2000, 275(52): 40904-40909. [16] Mark A，Hock T，Kapturczak MH，et al. Induction of heme oxygenase-1 modulates the profibrotic effects of transforming growth factor-beta in human renal tubular epitheltal cells[J]. Cell Mol Biol，2005，5 1(4): 357-362. -
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