Department of Internal Medicine, Hanover Medical School, Hanover, Germany.
Eur J Clin Invest. 2009 Sep;39(9):755-60. doi: 10.1111/j.1365-2362.2009.02165.x. Epub 2009 Jul 14.
Recent studies in mice experimental models with acute ischaemic injury revealed that erythropoietin (EPO) has numerous tissue-protective effects in the heart, brain and kidneys. We therefore explored the tissue-protective properties of chronic EPO treatment in an experimental model of the db/db mouse with diabetic heart injury.
We randomly treated 11 db/db mice with placebo (saline), 0.4 microg of the continuous erythropoietin receptor activator (CERA) per week (n = 11) or 1.2 microg CERA per week (n = 11) for 14 weeks, and analysed cardiac tissue. The lower CERA dose was a non-haematologically effective dose, whereas the second increased the haematocrit.
Compared with mice in the placebo group, CERA-treated mice had a reduction in TGF-beta(1) and collagen I expression in cardiac tissue (P < 0.01 vs. higher dose CERA). In addition, an increased expression of the pro-survival intracellular pathway p-AKT was observed (P < 0.05 vs. higher dose CERA). The values for the lower C.E.R.A had an intermediate nonsignificant effect. Furthermore, we were able to show that atrial natriuretic peptide (ANP) expression was increased in both CERA groups.
Chronic treatment with CERA protects cardiac tissue in diabetic animals, i.e. it inhibits molecular pathways of cardiac fibrosis, and the effects are dose-dependent.
最近在急性缺血损伤的小鼠实验模型中进行的研究表明，促红细胞生成素（EPO）对心脏、大脑和肾脏具有多种组织保护作用。因此，我们在糖尿病心脏损伤的 db/db 小鼠实验模型中探索了慢性 EPO 治疗的组织保护特性。
我们随机用安慰剂（生理盐水）、每周 0.4 微克持续红细胞生成素受体激活剂（CERA）（n = 11）或每周 1.2 微克 CERA（n = 11）治疗 11 只 db/db 小鼠 14 周，并分析心脏组织。较低的 CERA 剂量是一种非血液学有效剂量，而第二种剂量增加了血细胞比容。
与安慰剂组的小鼠相比，CERA 治疗的小鼠心脏组织中 TGF-β1 和胶原 I 的表达减少（P < 0.01 与高剂量 CERA）。此外，还观察到促生存细胞内途径 p-AKT 的表达增加（P < 0.05 与高剂量 CERA）。较低的 C.E.R.A 值具有中间非显著效应。此外，我们能够表明两种 CERA 组的心房利钠肽（ANP）表达均增加。
慢性 CERA 治疗可保护糖尿病动物的心脏组织，即抑制心脏纤维化的分子途径，且作用呈剂量依赖性。
