白藜芦醇通过缓解内质网应激治疗小鼠糖尿病

Resveratrol Treats Diabetes in Mice by Relieving Endoplasmic Reticulum Stress

该研究利用链脲佐菌素(streptozotocin,STZ)建立糖尿病小鼠模型,2周后成模,将小鼠随机分为3组:0μmol白藜芦醇组(DD)、10μmol白藜芦醇组(DR-10)、100μmol白藜芦醇组(DR-100),白藜芦醇腹腔注射给药。制作胰腺组织切片,之后进行HE和胰岛素免疫荧光染色,观察胰腺胰岛的体积及形态变化;利用血糖仪检测血糖的变化;qRT-PCR检测胰腺组织中内质网应激相关基因的变化;Western blot检测内质网应激相关蛋白的变化。结果表明,白藜芦醇腹腔注射3周后,模型小鼠的体质量没有发生明显的变化,而DR-10组和DR-100组的血糖水平有所下降,同时胰岛素的分泌量有所增加。通过分析小鼠胰腺组织的HE切片发现,DR-10和DR-100组胰岛中的细胞损伤降低。对小鼠胰腺组织切片进行免疫荧光染色发现,DR-10和DR-100组中分泌胰岛素的细胞数量明显增多。白藜芦醇促进了胰岛素、胰高血糖素、PDX1、C-Myc和Bcl-2基因的表达,降低了Grp78、CHOP以及Caspase 3基因的表达。综上所述,白藜芦醇通过缓解糖尿病模型小鼠胰腺的内质网应激,进而改善糖尿病小鼠的高血糖症状。

In this study,STZ(streptozotocin)was used to create a diabetic mouse model,which was modeled two weeks later.The mice were randomly divided into three groups,including 0μmol resveratrol group(DD),10μmol resveratrol group(DR-10),and 100μmol resveratrol group(DR-100).Resveratrol was given by intraperitoneal injection.HE and insulin immunofluorescence stainings of pancreatic tissue sections were performed to observe the changes in the volume and morphology of pancreatic islets.Using a blood glucose meter,the change of blood glucose was detected.Using qRT-PCR,the changes of endoplasmic reticulum stress-related genes in pancreatic tissues were measured.Western blot detected the changes of endoplasmic reticulum stress-related proteins.The results showed that after three weeks of intraperitoneal injection of resveratrol,the body masses of the model mice did not change significantly,the blood glucose levels of DR-10 and DR-100 groups decreased,and the amount of insulin secretion increased.Analysis of HE slices revealed that the cell damage in the pancreatic islets of DR-10 and DR-100 decreased.Immunofluorescence staining of mouse pancreas tissue sections revealed that the number of cells secreting insulin in DR-10 and DR-100 groups increased significantly.Resveratrol promotes the expression of insulin,glucagon,PDX1,C-Myc and Bcl-2,and reduces the expression of Grp78,CHOP and Caspase 3.In summary,resveratrol can alleviate the endoplasmic reticulum stress in the pancreas of diabetic model mice,thereby improving the symptoms of hyperglycemia in diabetic mice.