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胡芦巴碱通过过氧化物酶体增殖物激活受体γ减轻2型糖尿病大鼠的糖尿病肾病和胰岛素抵抗。

Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-γ.

作者信息

Li Yinyan, Li Qaobei, Wang Chunyan, Lou Zhe, Li Qingchang

机构信息

Department of Ultrasonic Diagnosis, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

出版信息

Exp Ther Med. 2019 Aug;18(2):1331-1337. doi: 10.3892/etm.2019.7698. Epub 2019 Jun 21.

DOI:10.3892/etm.2019.7698
PMID:31363374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6614738/
Abstract

Trigonelline has been reported to serve an important role in cell cycle control, oxidative and ultraviolet stress and DNA methylation. In the present study, the effects of trigonelline were examined on type-2 diabetes mellitus (T2DM)-induced renal dysfunction, and its possible mechanism was investigated. Sprague-Dawley rats were fed with high-fat diet (HFD) for 4 weeks and intraperitoneally injected with 35 mg/kg of streptozotocin for 4 weeks. As a result, trigonelline increased body weight, inhibited the kidney weight/body weight ratio and blood glucose levels, and reduced the levels of blood urea nitrogen, creatinine and albumin in type 2 diabetic rats. In addition, trigonelline also reduced inflammation, oxidative stress and kidney cell apoptosis in T2DM rats. In terms of the molecular mechanisms involved, trigonelline induced the protein expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppressed glucose transporter 4 but suppressed the protein expression of tumor necrosis factor-α and leptin in T2DM rats. The present results demonstrated that trigonelline reduced diabetic nephropathy and insulin resistance in T2DM rats through PPAR-γ.

摘要

据报道,胡芦巴碱在细胞周期调控、氧化应激和紫外线应激以及DNA甲基化中发挥重要作用。在本研究中,研究了胡芦巴碱对2型糖尿病(T2DM)诱导的肾功能障碍的影响,并探讨了其可能的机制。将Sprague-Dawley大鼠高脂饮食喂养4周,然后腹腔注射35 mg/kg链脲佐菌素,持续4周。结果显示,胡芦巴碱可增加2型糖尿病大鼠体重,抑制肾重/体重比及血糖水平,并降低血尿素氮、肌酐和白蛋白水平。此外,胡芦巴碱还可减轻T2DM大鼠的炎症、氧化应激及肾细胞凋亡。就其涉及的分子机制而言,胡芦巴碱可诱导过氧化物酶体增殖物激活受体(PPAR)-γ的蛋白表达,抑制葡萄糖转运蛋白4,但可抑制T2DM大鼠肿瘤坏死因子-α和瘦素的蛋白表达。目前的结果表明,胡芦巴碱可通过PPAR-γ减轻T2DM大鼠的糖尿病肾病及胰岛素抵抗。

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