基于Wnt7a/GSK-3β信号轴探讨左归丸改善妊娠糖尿病大鼠子代胰腺β细胞功能的机制OA

OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus(GDM).METHODS Thirty-six pregnant rats were divided into normal group,model group,insulin glargine group(positive control),and low-,medium-and high-dose Zuogui pill groups,with 6 rats in each group.The normal group and model group were given intragastric administration of equal-volume normal saline.The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg,and the dosage was increased by 1 U per day until random blood glucose returned to normal.The low-,medium-and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725,9.45 and 18.9 g/kg once a day until the birth of offspring.On postnatal day 21(12 offspring in each group),body weight,fasting blood glucose(FBG)and oral glucose tolerance test were performed on the offspring.Pancreatic histopathological changes of 60-day-old offspring were observed.The insulin-positive expression area ratio in pancreatic tissue,serum levels of glycated serum protein(GSP),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a(Wnt7a)and glycogen synthase kinase 3β(GSK-3β)in pancreatic tissue were detected.RESULTS Compared with normal group,the body weight,insulin-positive expression area ratio in pancreatic tissue,serum HDL-C level,and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group(P＜0.05).Meanwhile,FBG,blood glucose levels at 60,90 and 120 min after intragastric administration of 20%glucose solution,serum GSP and LDL-C levels,as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased(P＜0.05);mild degeneration and necrosis of islet cells were observed in pancreatic tissue.Compared with the model group,the above-mentioned indexes were significantly reversed in medium-and high-dose Zuogui pill groups(P＜0.05),and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis,so as to improve pancreatic β cell function in the offspring of GDM rats.