Therapeutic Effect of Alprostadil in Diabetic Nephropathy: Possible Roles of Angiopoietin-2 and IL-18
Therapeutic Effect of Alprostadil in Diabetic Nephropathy: Possible Roles of Angiopoietin-2 and IL-18
复制标题
前列地尔治疗糖尿病肾病的疗效：Angiopoietin-2 和 IL-18 的可能作用
DOI：
10.1159/000366309
复制
发表时间：
2014-01-01
影响因子：
--
通讯作者：
Wang, Yumei
中科院分区：
文献类型：
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作者：
Luo, Changqing;Li, Ting;Wang, Yumei
背景/目标：目的探讨血管生成素-2（Ang-2）和白细胞介素-18（IL-18）在糖尿病肾病（DN）发病中的作用及阿曲地尔保护肾功能的分子机制。方法：采用链脲佐菌素诱导糖尿病小鼠DN模型，腹腔注射阿糖胞苷。分别于给药后2、4、8周，采用逆转录聚合酶链反应（RT-PCR）、免疫印迹（Western blot）和免疫组化方法检测肾脏Ang-2和IL-18的mRNA和蛋白表达。将小鼠肾小球内皮细胞（GEnCs）在高糖中培养并用阿鲁地尔处理。用Ang-2-pcDNA和Ang-2-siRNA转染后，通过Western blot分析测量Ang-2和IL-18的表达。结果：Alcohedil治疗导致肾损害参数显著降低。Ang-2和IL-18在DN小鼠和高糖培养的GEnCs中均显著增加;然而，它们的表达被alcohydil治疗大大降低。Ang-2还可增加高糖环境下培养的内皮细胞IL-18的表达，Ang-2 siRNA可部分阻断这一效应。结论：Ang-2和IL-18可能与DN的发生、发展有关。阿替洛尔治疗可通过减少蛋白尿来保护肾功能。这些作用至少部分是通过下调Ang-2和IL-18表达介导的。
Background/Aims: To investigate the role of angiopoietin-2 (Ang-2) and IL-18 in the pathogenesis of diabetic nephropathy (DN) and the molecular mechanisms through which alprostadil protects renal function. Methods: DN was induced by streptozotocin and intraperitoneal injection of alprostadil was given to diabetic mice. After 2, 4 and 8 weeks of alprostadil treatment, the mRNA and protein expression of kidney Ang-2 and IL-18 were detected by reverse transcription PCR, Western blot and immunohistochemistry analyses. Mouse glomerular endothelial cells (GEnCs) were cultured in high glucose and treated with alprostadil. After transfection with an Ang-2-pcDNA and Ang-2-siRNA, both Ang-2 and IL-18 expression were measured by Western blot analyses. Results: Alprostadil treatment caused a significant decrease in the renal damage parameters. Both Ang-2 and IL-18 were significantly increased in DN mice and in GEnCs cultured in high glucose; however, their expression was greatly reduced by alprostadil treatment. Ang-2 could also increase IL-18 expression in cultured endothelial cells under high glucose, and this response was partially blocked by Ang-2 siRNA. Conclusions: Ang-2 and IL-18 may be associated with the development and progression of DN in mice. Alprostadil treatment can protect renal function by reducing proteinuria. These effects are mediated, at least in part, through down-regulation of Ang-2 and IL-18 expression.