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茯苓多糖调控SIRT1/FOXO3a通路对妊娠糖尿病大鼠胰岛素抵抗的影响 被引量:8

Impact of Poria polysaccharides on insulin resistance in gestational diabetic rats by regulating SIRT1/FOXO3a pathway
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摘要 目的探究茯苓多糖对妊娠糖尿病(GDM)大鼠胰岛素抵抗的影响以及对沉默信息调节因子2相关酶1(SIRT1)/叉头框转录因子O3a(FOXO3a)信号通路的调控机制。方法孕鼠在妊娠第2天尾连续静脉注射3 d链脲佐菌素(35 mg/kg)构建GDM模型。将造模成功后随机分为模型组、茯苓多糖-L(3 mg/kg)、茯苓多糖-M(6 mg/kg)、茯苓多糖-H(12mg/kg)剂量组、二甲双胍(20mg/kg)组。给药结束后,检测FBG、FINS,计算HOMA-IR;检测TC、TG、LDL-C、SOD、MDA、TNF-α、IL-6水平;H-E染色观察肝组织病理学变化;Westernblot法检测肝组织中SIRT1、FOXO3a蛋白表达。结果与对照组比较,模型组大鼠肝组织病变明显,炎性细胞大量浸润,组织损伤严重,FBG、FINS、HOMA-IR、TC、TG、LDL-C水平以及MDA、TNF-α、IL-6水平、FOXO3a蛋白表达均显著升高(P<0.05),SOD活性、SIRT1蛋白表达显著降低(P<0.05);与模型组比较,二甲双胍组与茯苓多糖各剂量组肝组织病变明显减轻,FBG、FINS、HOMA-IR、TC、TG、LDL-C水平以及MDA、TNF-α、IL-6水平、FOXO3a蛋白表达均显著降低(P<0.05),SOD活性、SIRT1蛋白表达显著上升(P<0.05),且茯苓多糖各剂量组间具有剂量效应(P<0.05);与二甲双胍组比较,茯苓多糖-H组上述指标无显著差异(P>0.05)。结论茯苓多糖可有效抑制炎症反应的发生,减轻氧化应激损伤,调节糖脂代谢,改善GDM大鼠胰岛素抵抗,可能与调节SIRT1/FOXO3a信号通路的表达有关。 Objective To explore the impact of Poria cocos polysaccharides on insulin resistance in gestational diabetes mellitus(GDM)rats and the regulatory mechanism on silent information regulator 2 homolog 1(SIRT1)/forkhead box O3a(FOXO3a)signaling pathway.Methods Pregnant rats were injected with streptozotocin 35 mg/kg via tail vein on the 2nd day of gestation for 3 days to establish a GDM model.Rats with successful modeling were randomly grouped into model group,Poria polysaccharide low(3 mg/kg),medium(6 mg/kg),high(12 mg/kg)dose groups,and metformin(20 mg/kg)group.After the administration,FBG,FINS were detected,and HOMA-IR was calculated.The levels of TC,TG,LDL-C,SOD,MDA,TNF-α,and IL-6 were measured.H-E staining was used to observe the pathological changes of liver tissue.Western blot method was used to detect the expression of SIRT1 and FOXO3a proteins in liver tissue.Results Compared with the control group,the model group showed obvious pathological changes in the liver tissue,disordered arrangement of liver cells,cytoplasmic pyknosis,massive infiltration of inflammatory cells,and severe tissue damage,the levels of FBG,FINS,HOMA-IR,TC,TG,LDL-C,MDA,TNF-α,IL-6 and the expression of FOXO3a protein were significantly increased(P<0.05),the SOD activity and the expression of SIRT1 protein were significantly decreased(P<0.05).Compared with the model group,the liver tissue lesions in the metformin group and the different doses of Poria polysaccharide groups were significantly reduced,the levels of FBG,FINS,HOMA-IR,TC,TG,LDL-C,MDA,TNF-α,IL-6 and the expression of FOXO3a protein were significantly decreased(P<0.05).The SOD activity and the expression of SIRT1 protein were significantly increased(P<0.05),and the dose effect of polysaccharide between groups was statistically significant(P<0.05).Tthere was no significant difference in the above indexes between the Poria polysaccharide-H group and the metformin group(P>0.05).Conclusion Poria polysaccharide can reduce inflammation and oxidative stress,regulate glucose and lipid
作者 杨娜 肖颖 刘静云 YANG Na;XIAO Ying;LIU Jingyun(Department of Obstetrics,Tangshan Central Hospital,Tangshan,Hebei063000,China)
出处 《中国优生与遗传杂志》 2022年第8期1371-1375,共5页 Chinese Journal of Birth Health & Heredity
关键词 茯苓多糖 妊娠糖尿病 胰岛素抵抗 沉默信息调节因子2相关酶1 叉头框转录因子O3a Poria polysaccharide gestational diabetes mellitus insulin resistance silent information regulator 2 homolog 1 forkhead box O3a
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