姜黄素通过Wnt/β-catenin信号拮抗肥胖致肾损伤

In recent years，the incidence of obesity-related glomerulopathy was significantly increased in China. It brought a serious economic burden to the individuals and their families. Till now, it is still lack of effective treatment for obesity-related glomerulopathy by drug. Curcumin is a phenolic substances extracted from Zingiberaceae turmeric, it may act directly on adipocyte, inhibiting expression of leptin, resistin, and inflammatory cytokine. It is also up-regulated expression of protective factor adiponectin and thus ameliorate obesity-related insulin resistance, hyperglycemia and hyperlipidemia. Our previous study found that curcumin could inhibit leptin-induced secretion of extracelluar cell matrix in mesengial cells. We also observed that curcumin can inhibit leptin-stimulated activation of Wnt/?-catenin signals. In this study, on the basis of our preliminary results, we will construct cell model of obesity- induced renal injury by leptin stimulation. We will explore the protective effect of curcumin on this cell model and the role of Wnt/?-catenin signaling in such process. We will further confirm the protective effect of curcumin and related mechanisms in animal model of obesity-induced renal injury. If this project is completed as expected, we will provide experimental basis of effective prevention and treatment of obesity-related glomerulopathy.

近年肥胖相关性肾小球病的发病率明显升高，给患者个人、家庭和社会造成严重负担，目前尚缺乏有针对性的药物治疗措施。姜黄素（curcumin）是从姜科植物姜黄中提取的一种酚类物质，它可直接作用于脂肪细胞，抑制瘦素，抵抗素，炎症细胞因子的表达，上调肥胖时具有保护作用的脂联素表达，从而抑制肥胖时出现的胰岛素抵抗，高血糖，高脂血症。我们前期研究结果发现姜黄素抑制瘦素引起的系膜基质分泌，同时观察到姜黄素可抑制瘦素引起的Wnt/β-catenin信号活化。本研究在我们前期实验基础上，拟以瘦素为刺激物，建立肥胖致肾损伤的细胞模型，研究中药提取物姜黄素对肥胖致肾损伤的细胞模型的保护作用，以Wnt/β-catenin信号通路为切入点研究姜黄素的作用机制；并进一步在动物实验中证实姜黄素在肥胖致肾损伤中的保护作用及其作用机制。本项目如能按预期完成，将为探寻有效的防治肥胖相关性肾小球病措施提供实验依据。

近年肥胖相关性肾小球病的发病率明显升高，给患者个人、家庭和社会造成严重负担，目前尚缺乏有针对性的药物治疗措施。姜黄素（curcumin）是从姜科植物姜黄中提取的一种酚类物质，它可直接作用于脂肪细胞，抑制瘦素，抵抗素，炎症细胞因子的表达，上调肥胖时具有保护作用的脂联素表达，从而抑制肥胖时出现的胰岛素抵抗，高血糖，高脂血症。我们研究结果发现姜黄素抑制瘦素引起的足细胞损伤，同时观察到姜黄素可抑制瘦素引起的Wnt/β-catenin信号活化，提示姜黄素可能通过Wnt/β-catenin信号通路上调肥胖时的保护因子，抑制肥胖相关的多种代谢异常。将为进一步探寻有效的防治肥胖相关性肾小球病措施提供实验依据。