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非经典途径IKKε和TBK1在炎症中的作用机制及药物治疗
非经典途径IKKε和TBK1在炎症中的作用机制及药物治疗
余美霞1,刘 迅2,江高峰3,倪 健4,周咏明5

1 武汉科技大学附属天佑医院妇产科,武汉 430064;2 中山大学附属第三医院肾内科,广州 510630; 3 武汉科技大学附属天佑医院中心实验室;4 美国哈佛医学院布里格母女子医院肿瘤临床药剂科, 波士顿MA02115;5 武汉科技大学附属天佑医院肾内科,武汉 430064
The mechanism of noncanonical IKKε and TBK1 pathway in the insulin resistance and obesity as well as drug therapy
(1 Department of Gynecology and Obstetrics, Affiliated Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064,China; 2 Division of Nephrology, Department of Internal Medicine, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; 3 Department  of Oncology Clinical Pharmacy, Brigham and Women's Hospital, Harvard Medicine School, Boston MA02115,USA; 4 Department of Nephrology, Affiliated Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064,China)

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起始页:1520

摘要:[摘要] 越来越多的研究发现非经典途径IKKε和TBK1在慢性炎症中起着重要作用,可促进慢性炎症细胞因子TNF-α和MCP-1等的表达,增加自身免疫性疾病和肺部炎症疾病的炎症反应,减少肥胖鼠脂肪细胞中的β-肾上腺素受体对儿茶酚胺的敏感性,降低第二信使cAMP的水平,而儿茶酚胺和cAMP均有加快能量消耗的作用。阻断IKKε和TBK1途径,可减少慢性疾病和肺部疾病的炎症反应,并减少脂肪细胞中慢性炎症因子的表达,增强胰岛素敏感性,减少胰岛素抵抗,减轻体重,起到治疗肥胖病和2型糖尿病的作用。因此,研究阻断IKKε和TBK1途径的药物治疗,对治疗慢性炎症疾病、肥胖病和2型糖尿病具有重大意义。

关键词:[关键词] IKKε;TBK1;胰岛素抵抗;2型糖尿病;药物治疗

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Abstract:[Abstract] More and More studies have demonstrated that thenoncanonical IKKε and TBK1 pathway play important roles in the chronic inflammation, by improving the expression of proinflammation TNF-α and MCP-1, decreasing β-adrenergic receptor of catecholamine sensitivity and reducing the level of the second messenger cAMP in fat cells of obese rat, while the function of catecholamine and cAMP involve speeding up energy consumption. Inhibiting IKKα and IKKβ pathway play roles in treating the obesity and type 2 diabetes mellitus through significantly reducing the expression of proinflammation cytokine in fat cells, increasing the insulin sensitivity and decreasing body weight. Blocking IKKε and TBK1 are of important significance for the treatment of obesity and type 2 Diabetes.

Key words:[Key words] IKKε;TBK1;insulin resistance; type 2 diabetes mellitus; drug therapy

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