Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy.
Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy.
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DOI：
10.1016/j.jep.2012.02.007
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发表时间：
2012-05
影响因子：
5.4
通讯作者：
Mianzhi Zhang;Miao Liu;M. Xiong;Junbo Gong;Xiaoyue Tan
中科院分区：
文献类型：
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作者：
Mianzhi Zhang;Miao Liu;M. Xiong;Junbo Gong;Xiaoyue Tan
民族药理相关性五味子在中药中广泛用于治疗肝、肾、心脏，目的研究五味子提取物（SE）对链脲佐菌素（STZ）致小鼠蛋白尿和足细胞损伤的影响及其机制。材料与方法：以5g/kg体重的日剂量对STZ诱导的糖尿病肾病小鼠经口给药7周。分别于实验第6周和第9周检测尿白蛋白/肌酐比值和尿白蛋白排泄率。肾小球硬化和细胞外基质沉积的程度通过过碘酸-六亚甲基四胺银和Masson三色染色来确定。通过足细胞标记物、肾母细胞瘤1和nephrin的免疫组织化学染色检测足细胞的数量和裂膈的完整性。通过蛋白质印迹和免疫组织化学染色检测α-平滑肌肌动蛋白、E-钙粘蛋白和纤溶酶原激活物抑制剂-1以评估上皮向间质转化（EMT）的水平。实时荧光定量PCR检测足细胞中E-cadherin、α-SMA和snail的mRNA水平。此外，SE减弱肾小球硬化症和保护足细胞损失和完整性的狭缝隔膜。结论SE对糖尿病肾病有一定的治疗作用。SE减轻蛋白尿和肾小球硬化的作用可能是通过抑制EMT来保护足细胞的完整性。
ETHNOPHARMACOLOGICAL RELEVANCESchisandra chinensis fruit is widely used in Chinese medicine for the treatment of hepatic, renal, heart, cerebrovascular and infectious diseases.AIM OF THE STUDYTo investigate the effects of Schisandra chinensis fruit extract (SE) on albuminuria and podocyte injury as well as the underlying mechanism in the mouse model of streptozotocin (STZ)-induced diabetic nephropathy and in cultured mouse podocyte cells.MATERIALS AND METHODSSE was orally administrated in STZ-induced diabetic nephropathy mice for 7 weeks, at a daily dose of 5g/kg body weight. The urinary albumin/creatinine ratio and urine albumin excretion rate were measured at the 6th and 9th week of the experiment. The extent of glomerulosclerosis and extracellular matrix deposition were determined by periodic acid-silver methenamine and Masson's trichrome staining. The amount of podocytes and the integrity of the slit diaphragm were detected by immunohistological staining of podocyte markers, Wilms’ tumor 1 and nephrin. Alpha-smooth muscle actin, E-cadherin and plasminogen activator inhibitor-1 were measured by western blot and immunohistological staining to evaluate the level of epithelial-to-mesenchymal transition (EMT). Real-time reverse transcription PCR was used to detect the mRNA level of E-cadherin, alpha-SMA and snail in cultured podocyte cells.RESULTSTreatment with SE significantly decreased the urine albumin excretion rate and urinary albumin/creatinine ratio. In addition, SE attenuated glomerulosclerosis and protected against podocyte loss and integrity of the slit diaphragm. Furthermore, SE effectively prevented the EMT of podocytes caused by diabetic nephropathy.CONCLUSIONSOur studies suggest that SE might be beneficial for diabetic nephropathy. The effects of SE on attenuating albuminuria and glomerulosclerosis are possibly mediated by preserving podocyte integrity through suppressing EMT.