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山茱萸苷可能通过调节血管生成和丝裂原活化蛋白激酶信号通路改善糖尿病肾病。

Cornuside Ameliorates Diabetic Nephropathy Possibly by Regulating Angiogenesis and MAPK Signaling.

作者信息

Xiang Fang, Li Xin, Hu Wei

机构信息

Department of Nephrology, Songshan General Hospital.

Department of Urology, Songshan General Hospital.

出版信息

Tohoku J Exp Med. 2025 May 28;266(1):87-95. doi: 10.1620/tjem.2024.J112. Epub 2024 Oct 24.

Abstract

Diabetic nephropathy (DN) is a prevalent diabetic complication seriously threatening patients' health and lives. Cornuside is an iridoid glycoside compound with various pharmacological properties. Nonetheless, whether cornuside has a protective effect against DN remains unillustrated. In this study, a rat model for DN was established by streptozotocin (STZ) injection. Rat podocytes were stimulated with high glucose (HG) to mimic a DN microenvironment in vitro. Several indicators linked to kidney function were evaluated. Periodic Acid-Schiff (PAS) and hematoxylin-eosin staining were implemented for renal histologic analysis. Immunofluorescence staining of CD31 was used for the detection of neovascularization. Western blotting was employed to assess levels of angiogenic factors and MAPK signaling-related proteins in the kidney or podocytes. The results showed that cornuside administration alleviated STZ-elicited renal dysfunction, as evidenced by the reduction in fasting blood glucose, proteinuria, serum creatinine, and blood urea nitrogen. Cornuside attenuated renal pathological lesions in DN rats. Cornuside repressed angiogenesis in DN rat kidney tissues and podocytes. Cornuside blocked MAPK signaling in HG-stimulated podocytes. In conclusion, cornuside alleviates renal injury in DN rats possibly by hindering angiogenesis and MAPK signaling.

摘要

糖尿病肾病(DN)是一种常见的糖尿病并发症,严重威胁患者的健康和生命。山茱萸苷是一种具有多种药理特性的环烯醚萜苷类化合物。然而,山茱萸苷对DN是否具有保护作用仍未阐明。在本研究中,通过注射链脲佐菌素(STZ)建立DN大鼠模型。用高糖(HG)刺激大鼠足细胞以在体外模拟DN微环境。评估了几个与肾功能相关的指标。采用过碘酸-希夫(PAS)染色和苏木精-伊红染色进行肾脏组织学分析。用CD31免疫荧光染色检测新生血管形成。采用蛋白质印迹法评估肾脏或足细胞中血管生成因子和MAPK信号相关蛋白的水平。结果表明,给予山茱萸苷可减轻STZ诱导的肾功能障碍,空腹血糖、蛋白尿、血清肌酐和血尿素氮的降低证明了这一点。山茱萸苷减轻了DN大鼠的肾脏病理损伤。山茱萸苷抑制DN大鼠肾组织和足细胞中的血管生成。山茱萸苷阻断HG刺激的足细胞中的MAPK信号传导。总之,山茱萸苷可能通过阻碍血管生成和MAPK信号传导减轻DN大鼠的肾损伤。

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