Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.
Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.
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Icariside II 可改善链脲佐菌素诱导的糖尿病大鼠的糖尿病肾病
DOI：
10.2147/dddt.s90060
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Xin Z
中科院分区：
文献类型：
--
作者：
Tian W;Lei H;Guan R;Xu Y;Li H;Wang L;Yang B;Gao Z;Xin Z
目的探讨淫羊藿苷II(ICA II)逆转链脲佐菌素(STZ)诱导的I型糖尿病大鼠糖尿病肾病的作用及其可能机制。方法用胸腺嘧啶核苷类似物5-乙炔基-2-脱氧尿苷(EDU)标记新生雄性SD大鼠，追踪内源性标记保留祖细胞(LRC)。8周龄大鼠48只，随机分为正常对照组(n=16)、糖尿病组(n=16)和糖尿病+ICAⅡ治疗组(DM+ICAⅡ，n=16)。用链脲佐菌素诱导糖尿病大鼠8周后，DM组和DM+ICA II组分别给予赋形剂或ICA II(5 mg/kg/d)治疗8周。检测血肌酐、24小时尿蛋白定量、血尿素氮、糖化血红蛋白，并检测肾组织中von Willebrand因子、丙二醛、转化生长因子-β、转化生长因子-β/结缔组织生长因子信号转导通路、增殖标志物Ki-67、肾组织EDU+LRCs的表达。结果糖尿病大鼠血肌酐、24小时尿蛋白定量、血尿素氮水平明显升高，正常肾小球比例显著降低，I、IIa、IIb、III肾小球比例明显增加，而ICA II可逆转上述变化。值得注意的是，ICA II可显著下调肾组织丙二醛和转化生长因子-β/Smad/CTGF信号转导水平，上调von Willebrand因子、Ki-67和EDU+LRCs的表达。结论ICAⅡ治疗可通过增加血管内皮细胞含量，下调转化生长因子-β/Smad/CTGF信号通路和氧化应激水平，促进肾皮质和髓质细胞的增殖，从而减轻STZ糖尿病大鼠的糖尿病肾病。这些有益的作用似乎是通过其抗氧化能力和内源性EDU+祖细胞募集到肾脏组织中而起作用的。
Purpose To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ)-induced type I diabetic rats. Methods Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues. Results Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney. Conclusion ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue.