Effect of COPTIDIS RHIZOMA-RHEI RADIX ET RHIZOMA on Pancreaticβ-Cell in GK Rats Based on Endoplasmic Reticulum Stress
Objective:To investigate the mechanism underlying the improvement of pancreatic β-cell function in Goto-Kakizaki(GK)rats by COP-TIDIS RHIZOMA-RHEI RADIX ET RHIZOMA based on the endoplasmic reticulum stress pathway.Methods:The spontaneous GK rats that met the modeling criteria were randomly divided into model control group,metformin(0.1 g/kg)group,and COPTIDIS RHIZOMA-RHEI RADIX ET RHIZOMA(2.36 g/kg group and 4.72 g/kg)groups,and normal Wistar rats were selected as normal control group,with 6 in each group.After 8 weeks of intervention,HE staining was performed to observe the pathological changes of pancreas in rats.ELISA was used to measure insulin(INS)in pancreatic tissue.Real-time PCR was used to detect the mRNA expressions of pancreatic and duodenal ho-meobox 1(Pdx1)and glucose regulatory protein 78(Grp78)in pancreatic tissue.The expressions of glucose transporter protein 2(GLUT2)and GRP78 proteins in pancreatic tissue were detected by IHC method,while those of phosphorylated inositol-requiring enzyme1α(p-IRE1α)and phosphorylation of eukaryotic initiation factor 2α(p-EIF2α)proteins were detected by Western blot.Results:Compared with the normal control group,the model control group presented disordered structure of islets and reduced number of islet cells with inflammatory cell infiltra-tion.Additionally,the INS level and Pdx1 mRNA and GLUT2 protein expressions in pancreatic tissue were decreased(P＜0.01),while Grp78 mRNA and protein expressions and the expressions of p-IRE1α and p-EIF2α proteins were up-regulated(P＜0.01).Compared with the model control group,the COPTIDIS RHIZOMA-RHEI RADIX ET RHIZOMA(2.36 g/kg group and 4.72 g/kg)groups improved the morphological structure of islets in rats,and the INS level and Pdx1 mRNA and GLUT2 protein expressions in pancreatic tissue were elevated(P＜0.05),while Grp78 mRNA and protein expressions and the expressions of p-IRE1α and p-EIF2α proteins were decreased(P＜0.05),with the concentration of 2.36 g/kg exhibiting better effect.Conclusion:COPTIDIS RHIZOMA-RHEI RADIX ET RHIZOMA may exert a therapeutic effect on type 2 diabetes mellitus(T2DM)by inhibiting endoplasmic reticulum stress and improving pancreatic β-cell function.
万方数据
维普
