青钱柳多糖对糖尿病小鼠的保护作用及机制

Protective Effects and Mechanism of Cyclocarya Paliurus Polysaccharides on Diabetic Mice

目的探讨青钱柳多糖(cyclocarya paliurus polysaccharides,CPP)对链脲佐菌素(streptozotocin,STZ)诱导糖尿病(diabetes mellitus,DM)小鼠的降糖作用及可能的作用机制。方法采用腹腔注射STZ的方式制备DM小鼠模型,CPP高、中及低剂量组分别灌胃给予相应的CPP,阳性组灌胃给予盐酸二甲双胍,持续2周。期间记录小鼠一般状况,并于第0、7、14天测定体质量、空腹血糖(fasting blood glucose,FBG)及口服葡萄糖耐量(oral glucose tolerance,OGT);2周后生化仪测定血清生化指标;ELISA法检测血清胰岛素、C肽水平;对小鼠胰腺组织进行HE染色,观察其病理改变;免疫组化法检测小鼠胰腺组织中沉默信息调节因子1(silent information regulator 1,Sirt1)和腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)的表达;Western blot法检测胰腺组织中核因子E2相关因子(nuclear factor erythroid2-related factor,Nrf2)蛋白水平。结果与正常组比较,模型组小鼠FBG、血糖曲线下面积(area under curve,AUC)、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、肌酐(creatinine,CRE)、丙二醛(malondialdehyde,MDA)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的含量显著升高(P<0.01),高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、超氧化物歧化酶(superoxide dismutase,SOD)的含量及活力明显下降(P<0.01),C肽及胰岛素含量均下降;胰腺结构紊乱,胰腺组织中Sirt1、Nrf2及磷酸化AMPK(phosphorylated AMPK,p-AMPK)蛋白表达明显减低(P<0.05);经过14 d药物干预,与模型组比较,CPP各剂量组的血清学指标均有明显改善,HDL-C、C肽及胰岛素含量均有明显恢复(P<0.05),可见CPP对胰腺损伤具有明显的保护作用。结论CPP可有效降低糖尿病小鼠的血糖,改善胰腺组织损伤,其机制可能与CPP激活Sirt1/AMPK/Nrf2信号通路有关。

Objective To investigate the hypoglycemic effect of cyclocarya paliurus polysaccharides(CPP)on streptozotocin(STZ)-induced diabetic mice and the possible mechanisms involved.Methods Diabetic mouse models were prepared by intraperitoneal injection of STZ.The high,medium,and low dose groups of CPP were orally administered with corresponding CPP doses,and the positive control group was orally administered metformin hydrochloride for 2 weeks.The general condition of the mice was recorded during this period,and body weight,fasting blood glucose(FBG),and oral glucose tolerance(OGT)were measured on days 0,7,and 14.Biochemical indicators in serum were measured using a biochemical analyzer after 2 weeks.ELISA was used to detect serum insulin and C-peptide levels.Pancreatic tissue from the mice was stained with HE for pathological examination.Immunohistochemistry was used to detect the expression of silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)in pancreatic tissue.Western blot was used to measure the protein levels of nuclear factor erythroid2-related factor(Nrf2)in pancreatic tissue.Results Compared to the normal group,the FBG,area under the blood glucose curve(AUC),total cholesterol(TC),triglycerides(TG),creatinine(CRE),malondialdehyde(MDA),low-density lipoprotein cholesterol(LDL-C)levels and activities were significantly increased in the model group(P<0.01),while high-density lipoprotein cholesterol(HDL-C)and superoxide dismutase(SOD)activities were significantly decreased(P<0.01).C-peptide and insulin levels were also decreased.The pancreatic structure was disrupted,and the protein expression of Sirt1,Nrf2,and phosphorylated adenosine monophosphate-activated protein kinase(p-AMPK)in pancreatic tissue was significantly reduced(P<0.05).After 14 days of drug intervention,compared to the model group,the serum indicators in all CPP dose groups showed significant improvement,with notable recovery in HDL-C,C-peptide,and insulin levels(P<0.05),indicating a significant protective effect of CPP on pancreatic damage.Conclusion CPP can effectively reduce blood glucose levels in diabetic mice,improve pancreatic tissue damage,and its mechanism may be related to the activation of the Sirt1/AMPK/Nrf2 signaling pathway by CPP.