桑叶黄酮对糖尿病小鼠胰岛素抵抗及炎症反应的作用机制  

Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice

作　　者：许光远 张晓明[1] 贾春玲 XU Guangyuan;ZHANG Xiaoming;JIA Chunling(Fuxing Hospital of Capital Medical University,Beijing 100045,China)

机构地区：[1]首都医科大学附属复兴医院,北京100045

出　　处：《中国实验方剂学杂志》2023年第16期52-57,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金青年基金项目(82104614);北京市自然科学基金项目(7204268);北京市中医药科技发展基金项目(QN2018-35018);北京中医药薪火传承3+3工程张晓明基层老中医传承工作室;北京市临床中医重点专科培育项目。

摘　　要：目的:观察桑叶黄酮降糖、改善胰岛素抵抗、抗炎作用并探讨其作用机制。方法:6~7周龄雄性db/db小鼠随机分为模型组、桑叶黄酮高、低剂量组(1.00、0.50 g·kg^(-1)·d^(-1)),另设同周龄C57BL小鼠为正常组。干预6周后,检测小鼠空腹血糖(FBG)、血清胰岛素水平(Fins)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、游离脂肪酸(FFA)、血肌酐(SCr)、血尿素氮(BUN)、天门冬氨酸氨基转移酶(AST)、计算胰岛素抵抗指数(HOMA-IR);检测肝脏超氧化物歧化酶(SOD)、谷胱甘肽过氧物酶(GSH-Px)、过氧化氢酶(Catalase);苏木素-伊红(HE)染色检测小鼠肝脏形态结构变化;蛋白免疫印迹法(Western blot)检测肝脏环氧合酶-2(COX-2)、一氧化氮合酶(iNOS)、核转录因子-κB(NF-κB)蛋白表达。结果:与模型组比较,桑叶黄酮高、低剂量组FBG、Fins、HOMA-IR、IL-6、TNF-α、FFA水平明显降低(P<0.05,P<0.01);肝脏SOD、GSH-Px、Catalase水平明显升高(P<0.05,P<0.01);与模型组比较,桑叶黄酮高、低剂量组HE染色显示肝细胞排列整齐,炎细胞浸润及细胞脂肪样变明显改善;与模型组比较,桑叶黄酮高、低剂量组肝脏COX-2、iNOS、NF-κB蛋白表达明显降低(P<0.05,P<0.01)。结论:桑叶黄酮具有降糖、改善胰岛素抵抗作用,其作用可能是通过调控糖尿病小鼠肝脏NF-κB分子影响COX-2、iNOS及炎症因子释放,改善炎症状态实现的。Objective:To observe the glucose-lowering,insulin resistance-improving,and antiinflammatory effects of flavonoids from mulberry leaves(FML)and explore their underlying mechanism.Method:Male db/db mice aged 6-7 weeks were randomly divided into a model group,a high-dose FML group(1.00 g·kg·d^(-1)),and a low-dose FML group(0.50 g·kg^(-1)·d^(-1)).C57BL mice of the same age were assigned to the normal group.After six weeks of intervention,fasting blood glucose(FBG),serum fasting insulin levels(Fins),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),free fatty acid(FFA),blood creatinine(SCr),blood urea nitrogen(BUN),and aspartate aminotransferase(AST)levels were measured,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase activities in the liver were measured.Morphological changes in the liver were assessed by hematoxylin-eosin(HE)staining.The protein expression of cyclooxygenase-2(COX-2),inducible nitric oxide synthase(iNOS),and nuclear factor-κB(NF-κB)in the liver was detected by Western blot.Result:Compared with the model group,the high-dose and low-dose FML groups showed significant reductions in FBG,Fins,HOMA-IR,IL-6,TNF-α,and FFA levels(P<0.05,P<0.01),and increased levels of SOD,GSH-Px,and catalase in the liver(P<0.05,P<0.01).HE staining of the liver in the FML groups showed improved arrangement of hepatocytes,reduced inflammatory cell infiltration,and alleviated cellular steatosis compared with the model group.The protein expression of COX-2,iNOS,and NF-κB in the liver significantly decreased in the FML groups as compared with that in the model group(P<0.05,P<0.01).Conclusion:FML have glucose-lowering and insulin resistance-improving effect,which may be attributed to their regulation of the NF-κB pathway in the liver of diabetic mice,leading to the suppression of the release of COX-2,iNOS,and inflammatory cytokines,thereby improving the inflammatory state.

关 键 词：桑叶黄酮 2型糖尿病 胰岛素抵抗 炎症 环氧合酶-2(COX-2) 一氧化氮合酶(iNOS) 核转录因子-κB(NF-κB) 

分 类 号：R2-0[医药卫生—中医学] R22R242R2-031R285.5