山奈酚通过抑制NLRP3炎症小体介导的脂肪组织炎症改善db/db小鼠胰岛素抵抗发生  

Improvement of Insulin Resistance by Kaempferol in db/db Mice based on Supression of NLRP3 Inflammasome Mediated Adipose Tissue Inflammation

作　　者：翟慧媛[1] 王东旭[1] 顾宏伟 鞠娟[1] 王勇[1] 袁亮亮 王超[1] 陈磊垚[1] ZHAI Huiyuan;WANG Dongxu;GU Hongwei;JV Juan;WANG Yong;YUAN Liangliang;WANG Chao;CHEN Leiyao(Nanjing Integrated Traditional Chinese and Western Medicine Hospital,Nanjing 210014,China)

机构地区：[1]南京中医药大学附属南京市中西医结合医院,南京210014

出　　处：《药学与临床研究》2023年第6期497-501,共5页Pharmaceutical and Clinical Research

基　　金：江苏省中医药管理局中医药科技发展计划项目(YB2020034);“南京药学会-常州四药医院药学科研基金”资助项目(2021YX032);南京市中医药科技专项(ZYYB202215)。

摘　　要：目的:探讨山奈酚能否通过调控肥胖小鼠脂肪组织炎症改善胰岛素抵抗发生并研究作用机制。方法:db/m小鼠作为对照组,db/db雄性小鼠随机分为模型组、二甲双胍组(0.15 g·kg^(-1)·d^(-1))和山奈酚组(50 mg·kg^(-1)·d^(-1))。连续灌胃给药6周,每周记录小鼠体重,6周后进行葡萄糖耐量试验、胰岛素耐量试验、皮下和附睾白色脂肪组织质量测定;HE染色观察脂肪组织形态学变化,免疫组化法观察巨噬细胞向脂肪组织的浸润程度及巨噬细胞标志物F4/80的表达,实时荧光定量PCR检测TNF-α和IL-18以及Arg-1和IL-10的mRNA表达,蛋白质免疫印迹试验检测NLRP3、pro-caspase1、cle-caspase1和IL-1β表达。结果:与模型组相比,山奈酚能够显著抑制db/db小鼠脂肪质量增加,抑制脂肪细胞肥大。山奈酚组小鼠脂肪组织巨噬细胞浸润减少,TNF-α和IL-18 mRNA表达减少,Arg-1和IL-10 mRNA表达增加;山奈酚治疗能够抑制小鼠附睾脂肪组织NLRP3、caspase1以及IL-1β表达,抑制NLRP3炎症小体激活。结论:山奈酚可以通过抑制NLPR3炎症小体介导的脂肪组织炎症改善db/db小鼠胰岛素抵抗的发生。Objective:To explore the mechanism of kaempferol in improving obesity-related insulin resistance and inflammation in the adipose tissues of obese mice.Methods:The db/db mice were divided into db/db group,kaempferol group(50 mg·kg^(-1)·d^(-1))and metformin group(0.15 g·kg^(-1)·d^(-1)),while the db/m mice were used as control group.Mice received continuous gavage of indicated treatments for 6 weeks,changes in body weights were recorded every week during the experimental period.At the end of experiment,epididymal and subcutaneous fat mass were analyzed;intraperitoneal glucose tolerance and insulin tolerance tests were carried out;the morphological changes of adipose tissues were observed by HE staining;macrophage infiltration degrees in the adipose tissues were observed by immunohistochemical staining;the expression of TNF-α,IL-1β,Arg-1 and IL-10 were detected by real-time PCR;and Western blots were performed to determine the protein levels of NLRP3,pro-caspase1,cle-caspase1 and IL-1β.Results:Kaempferol treatment for 6 weeks significantly reduced the increase of body weight,fat mass and adipocyte size,and improved abnormal glucose tolerance and insulin resistance in the db/db mice.The macrophage infiltration decreased,and the mRNA expression were downregulated for TNF-αand IL-1βwhile upregulated for Arg-1 and IL-10 in the adipose tissues of obese mice treated with kaempferol.Kaempferol treatment significantly decreased the protein expression of NLRP3,pro-caspase1,cle-caspase1 and IL-1β.Conclusion:Kaempferol improves obesity-related insulin resistance in db/db mice by regulating NLRP3 inflammasome mediated adipose tissue inflammation.

关 键 词：山奈酚 DB/DB小鼠 脂肪组织炎症 肥胖 胰岛素抵抗 

分 类 号：R966[医药卫生—药理学]