Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.
Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.
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DOI：
10.1089/jmf.2011.1921
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发表时间：
2012-05
影响因子：
2.4
通讯作者：
Lei Zhou;X. An;S. Teng;Jingshun Liu;Wen-Bin Shang;Ai-Hua Zhang;Yang-Gang Yuan;Jiang-yi Yu
中科院分区：
文献类型：
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作者：
Lei Zhou;X. An;S. Teng;Jingshun Liu;Wen-Bin Shang;Ai-Hua Zhang;Yang-Gang Yuan;Jiang-yi Yu
糖尿病肾病（DN）是糖尿病的重要并发症，足细胞凋亡在DN的发生发展中起着重要作用。本研究观察了黄蜀葵花总黄酮甙（TFA）对实验性糖尿病肾病大鼠尿微量白蛋白和肾小球足细胞凋亡的预防作用。预先口服TFA（200 mg/kg/d）24周可显著降低链脲佐菌素诱导的DN大鼠的尿微量白蛋白/肌酐比值和24 h尿总蛋白。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法显示TFA预处理可明显改善DN大鼠肾小球细胞凋亡。荧光激活细胞分选和Hoechst 33342染色结果表明，以金丝桃苷（50和200 μg/mL）作为TFA的主要活性成分预孵育足细胞，可显著减轻晚期糖基化终产物（AGEs）诱导的足细胞凋亡。Western blot分析表明，增加caspase-3和caspase-8的表达诱导AGEs也抑制预处理金丝桃苷在两个剂量。我们的研究结果表明，TFA预处理可以减少早期DN的尿白蛋白排泄，这可能是通过防止肾损害和足细胞凋亡来实现的。
Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 μg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.