Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: Attenuation with renin-angiotensin blockade
Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: Attenuation with renin-angiotensin blockade
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DOI：
10.1111/j.1440-1797.2003.00227.x
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发表时间：
2004-02-01
期刊：
影响因子：
2.5
通讯作者：
Gilbert, RE
中科院分区：
文献类型：
--
作者：
Kelly, DJ;Stein-Oakley, A;Gilbert, RE
背景和目的：肾小管萎缩是大多数肾脏疾病的主要特征，与肾功能丧失密切相关。本研究旨在探讨Fas/FasL诱导的肾小管上皮细胞凋亡是否是实验性糖尿病肾病的一个特征。方法：6周龄雌性Ren-2大鼠注射链脲佐菌素，维持糖尿病12周。进一步组糖尿病大鼠进行治疗的血管紧张素转换酶抑制剂，培哚普利，为12 weeks.Results：广泛的细胞凋亡，确定通过使用介导的末端dUTP缺口末端标记（TUNEL）染色的糖尿病Ren-2大鼠的肾小管。这些变化与肾小管内Fas mRNA和Fas L（配体）的增加有关（P < 0.01）。培哚普利（6 mg/kg·d）治疗Ren-2大鼠后，肾小管上皮细胞凋亡明显减少，Fas mRNA和Fas L蛋白表达明显减少（P < 0.05）。结论：Fas/Fas L诱导的肾小管上皮细胞凋亡是糖尿病Ren-2大鼠的特征，阻断RAS可减轻Fas/Fas L诱导的肾小管上皮细胞凋亡。
Background and Aim: Tubular atrophy is a major feature of most renal diseases and is closely associated with the loss of renal function. The present study sought to investigate whether Fas/FasL-induced tubular epithelial cell apoptosis was a feature of experimental diabetic nephropathy. The effects of renoprotective therapy with blockade of the renin-angiotensin (RAS) system were also examined.Method: Six-week-old female Ren-2 rats were injected with streptozotocin and maintained diabetic for 12 weeks. Further groups of diabetic rats were treated with the angiotensin-converting enzyme inhibitor, perindopril, for 12 weeks.Results: Widespread apoptosis, identified by using mediated Terminal dUTP nick-end labelling (TUNEL) staining was noted in the tubules of diabetic Ren-2 rats. These changes were associated with an increase in both Fas mRNA and Fas L (ligand) within the tubules (P < 0.01). Treatment of diabetic Ren-2 rats with perindopril (6 mg/kg per day) reduced the apoptosis to control levels and was associated with a reduction in Fas mRNA and Fas L protein (P < 0.05).Conclusion: In conclusion, Fas/Fas L-induced tubular apoptosis is a feature of diabetic Ren-2 rats and is attenuated by the blockade of the RAS.