文档介绍：EPO对早期糖尿病大鼠肾脏的保护作用
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【摘要】目的观察亚临床剂量EPO对糖尿病大鼠早期肾损伤的影响,并探讨其作用机制。方法将大鼠随机分为正常对照组(NC)、糖尿病组(DM)及糖尿病EPO干预的两个剂量亚组(DMTA和DMTB)。采用链脲佐菌素诱导1型糖尿病大鼠模型,腹腔注射EPO 10周后,测定血糖、血压、血红蛋白、肾功能;光镜及电镜下观察肾组织形态学变化;免疫组化分析肾组织细胞凋亡相关蛋白Bcl2/Bax及细胞因子VEGF的表达。结果实验剂量EPO干预后,大鼠肾功能及其形态学指标得到显著改善;Bcl2/Bax比值及VEGF表达升高;均呈剂量依赖性。血糖、血压、血红蛋白值与对照组相比无明显变化。结论亚临床剂量EPO可延缓早期糖尿病肾病发展进程,可能与上调Bcl2/Bax蛋白表达比值,抑制肾脏细胞凋亡有关;在本实验条件下,肾组织VEGF的表达上调未对糖尿病肾病造成不良影响。
【关键词】糖尿病肾病;促红细胞生成素;细胞凋亡;Bcl2/Bax;血管内皮生长因子;大鼠
ABSTRACT: Objective To study the effect of subclinical dosage of EPO on early renal lesions of diabetic rats. Methods The rats were randomly divided into normal control group (NC), diabetic group (DM), diabetic rats treated with Adosage EPO (DMTA), and diabetic rats treated with Bdosage EPO (DMTB). Diabetic rats induced by STZ were given EPO intraperitoneally for 10 weeks; then blood glucose, blood pressure, renal function indexes, renal morphological parameter, the expression of cell apoptosis associated protein Bcl2/Bax and VEGF were measured. Results After treatment of EPO, renal functional and morphological indexes were improved significantly and the ratio of Bcl2/Bax and VEGF increased, both in a dosedependent manner. Blood sugar, blood pressure and hemoglobin concentration had no significant differences. Conclusion Subclinical dosage of EPO could play an advantageous role in diabetic nephropathy. Inhibition of cell apoptosis by upregulation of Bcl2/Bax expression rate may be responsible for renal protective effects despite the upregulation of VEGF.
KEY WORD: diabetic nephropathy; EPO; cell apoptosis; Bcl2/Bax; VEGF; rat
贫血在糖尿病人群中高发,包括糖尿病早期无明显肾损害的患者[1]。大量研究证实,贫血与糖尿病的微血管及大血管病变的产生和发展,以及患者的住院率和死亡率均有关系,是判断糖尿病及其并发症预后的一大危险因素[2]。糖尿病合并贫血的患者多存在EP
O的绝对或相对缺乏[1]。应用外源性EPO治疗时,除了纠正贫血,对早期糖尿病肾病(diabetic nephropathy, DN)发生发展的影响,国内外尚缺乏相关报道。本实验观察亚临床剂量EPO干预对早期DN动物模型的肾功能及肾组织形态学影响,并通过凋亡相关蛋白Bcl2/Bax及血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达来探讨其部分作用机制。
1 材料与方法
试剂与仪器