归龙丸通过Mfn2/PERK途径抑制链脲佐菌素诱导的糖尿病大鼠β细胞凋亡OA

Objective To investigate the effects of GuiLongWan(GLW)on pancreatic β-cell injury and apop-tosis in type 2 diabetes mellitus(T2DM)and to explore its underlying mechanisms.Methods A rat model of T2DM was established using streptozotocin(STZ),followed by oral administration of GLW or metformin.Fasting blood glucose and fasting insulin levels were measured.Hematoxylin and eosin(HE)staining,immunofluorescence staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining were performed to evaluate the path-ological changes and apoptosis of pancreatic β-cells.An H2O2-induced MIN6 cell injury and apoptosis model was es-tablished,and cells were treated with GLW-containing serum.Immunofluorescence colocalization,Western blotting,and co-immunoprecipitation(co-IP)were performed to assess the expression and interactions of proteins involved in the Mfn2/PERK pathway,as well as the apoptosis-related proteins Bcl-2 and Bax.Results In the animal experiments,STZ significantly increased pancreatic islet β-cell apoptosis,whereas GLW significantly alleviated STZ-induced β-cell apoptosis and reduced the apoptotic area,with an effect comparable to that of metformin.In vitro,GLW-containing ser-um significantly attenuated H2O2-induced β-cell apoptosis,increased Bcl-2 expression,decreased Bax expression,and alleviated endoplasmic reticulum stress-induced calcium overload.Furthermore,GLW-containing serum signifi-cantly inhibited PERK expression and the formation of the Mfn2-PERK complex,reduced H2O2-induced calcium over-load,and decreased MIN6 cell apoptosis.Conclusion GLW exerts a protective effect against pancreatic β-cell apopto-sis in diabetic rats by alleviating endoplasmic reticulum stress and calcium overload.Its mechanism may be associated with modulation of the interaction between Mfn2 and PERK,suggesting a potential pharmacological role of GLW in the treat-ment of T2DM.