柴胡皂苷D对2型糖尿病大鼠胰岛素抵抗及FoxO1/PGC-1α通路的影响  

Effects of saikosaponin D on insulin resistance and FoxO1/PGC-1αpathway in type 2 diabetic rats

作　　者：宋萍[1] 纳娜[2] 王燕[3] SONG Ping;NA Na;WANG Yan(Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学,银川750004 [2]银川市第一人民医院药学部,银川750003 [3]银川市第一人民医院内分泌科,银川750003

出　　处：《中国免疫学杂志》2023年第7期1425-1430,共6页Chinese Journal of Immunology

基　　金：宁夏医科大学校级科研项目(XT201414)。

摘　　要：目的:探讨柴胡皂苷D对2型糖尿病大鼠胰岛素抵抗及叉头框蛋白O1(FoxO1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)通路的影响。方法:以高脂饮食联合小剂量链脲佐霉素腹腔注射诱导建立2型糖尿病大鼠模型,随机分为模型组、柴胡皂苷D低剂量、中剂量、高剂量(50、100、150 mg/kg)组、二甲双胍(24.2 mg/kg)组,每组12只,另取12只SD大鼠以基础饲料喂养,并腹腔注射等剂量生理盐水,设为对照组。大鼠经药物分组处理后,测定大鼠空腹胰岛素(FINS)水平、空腹血糖(FBG)水平,计算胰岛素抵抗指数(IRI)、胰岛素敏感指数(ISI);行口服葡萄糖耐量试验(OGTT),计算血糖曲线下面积(AUC);检测大鼠肝糖原及肝脏脂肪合成情况;ELISA检测大鼠血清致炎因子水平;Western blot检测大鼠肝组织FoxO1/PGC-1α通路蛋白表达。结果:与对照组比较,模型组大鼠肝糖原显著减少,脂肪合成显著增多,FINS、FBG、IRI、AUC、血清TNF-α、IL-1β、IL-6、IL-18水平、肝组织FoxO1/PGC-1α通路p-FoxO1/FoxO1、PGC-1α蛋白表达水平显著升高,ISI水平显著降低(P<0.05);与模型组比较,柴胡皂苷D各剂量组与二甲双胍组大鼠肝糖原增多,脂肪合成减少,FINS、FBG、IRI、AUC、血清TNF-α、IL-1β、IL-6、IL-18水平、肝组织FoxO1/PGC-1α通路p-FoxO1/FoxO1、PGC-1α蛋白表达水平降低,ISI升高,且柴胡皂苷D各剂量组间呈剂量依赖性(P<0.05);柴胡皂苷D高剂量组与二甲双胍组比较,大鼠各指标无明显差异(P>0.05)。结论:柴胡皂苷D可能通过抑制FoxO1/PGC-1α信号通路激活从而降低血糖,抑制炎症,降低2型糖尿病大鼠胰岛素抵抗。Objective:To investigate the effects of saikosaponin D on insulin resistance and forkhead box protein O1(FoxO1)/peroxlsome proliferator-activated receptor-γcoactlvator-1α(PGC-1α)pathway in type 2 diabetic rats.Methods:The type 2 diabetes rat model was established by high-fat diet combined with small dose of streptozotocin by intraperitoneal injection.The rats were ran-domly divided into model group,low-dose saikosaponin D(50 mg/kg)group,medium-dose saikosaponin D(100 mg/kg)group and high-dose saikosaponin D(150 mg/kg)group,metformin(24.2 mg/kg)group,with 12 rats in each group,another 12 SD rats were fed with basal feed and intraperitoneally injected with the same dose of normal saline,as control group.After grouping and treatment with drugs,the fasting insulin(FINS)level and fasting blood glucose(FBG)level of rats were measured,and the insulin resistance index(IRI),insulin sensitivity index(ISI)were calculated.An oral glucose tolerance test(OGTT)was carried out,the area under the blood glucose curve(AUC)was calculated.The rat liver glycogen and liver fat synthesis were detected.The serum inflammatory factors levels in rats were detected with ELISA.The FoxO1/PGC-1αpathway protein expression in rat liver tissues was detected with Western blot.Results:Compared with control group,the liver glycogen of the model group reduced significantly,fat synthesis in-creased significantly,FINS,FBG,IRI,AUC,serum TNF-α,IL-1β,IL-6,IL-18 levels,and liver tissue FoxO1/PGC-1αaccess pFoxO1/FoxO1 and PGC-1αprotein expression increased significantly,ISI decreased significantly(P<0.05).Compared with model group,the liver glycogen of the saikosaponin D group and metformin group was increased,fat synthesis was reduced significantly,FINS,FBG,IRI,AUC,serum TNF-α,IL-1β,IL-6,IL-18 levels,liver tissue FoxO1/PGC-1αaccess p-FoxO1/FoxO1 and PGC-1αprotein expression were reduced significantly,white ISI was increased,and the saikosaponin D dosage groups were dose-dependent(P<0.05).Compared with the high-dose Saikosaponin D group and the m

关 键 词：柴胡皂苷D 2型糖尿病 胰岛素抵抗 FoxO1/PGC-1α通路 

分 类 号：R587.1[医药卫生—内分泌]