Objective:To explore the effect and mechanism of naringenin (NAR) on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes mellitus (GDM) .Methods:10 normal pregnant rats were selected as the control group, and the GDM model was prepared. One-time tail iv streptozotocin (STZ, 35 mg/kg) was used to construct GDM model. The 50 rats successfully modeled were divided into model group, metformin group (Met group, 20 mg/kg), low NAR (NAR-L, 50 mg/kg), high (NAR-H, 100 mg/kg) dose groups and NAR+EX527 group (NAR 100 mg/kg+EX527 10 mg/kg), 10 rats per group. Rats in Met group and NAR low-dose and high-dose groups were given corresponding doses of drugs ig. Rats in NAR+EX527 group were given NAR ig and EX527 ip at the same time, once a day, for 28 consecutive days. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) in rats were detected, and the homeostasis model assessment for insulin resistance (HOMA-IR) was calculated; the levels of serum triglycerides (TG), cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were detected; the level of malondialdehyde (MDA) in pancreatic tissue and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected; the tissue lesions of pancreas and placenta were observed with HE staining; the expression of pancreatic tissue AMP-activated protein kinase (AMPK), p-AMPK, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1 α) proteins was detected with Western blotting method. Results:Compared with control, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the model group were significantly increased, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly reduced ( P<0.05), and the placenta and pancreas tissues showed obvious pathological damage; Compared with the model group, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the Met group and the NAR-L and NAR-H groups were significantly reduced, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly increased ( P<0.05), the placenta and pancreas tissues damage reduced; and on the basis of NAR intervention, the use of SIRT1 inhibitor EX527 could significantly reverse the protective effect of NAR on GDM rats. Conclusion:NAR may improve glucose and lipid metabolism disorder and oxidative stress response in GDM rats by activatin SIRT1/PGC-1 α pathway.

Objective:To explore the effect and mechanism of naringenin (NAR) on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes mellitus (GDM) .Methods:10 normal pregnant rats were selected as the control group, and the GDM model was prepared. One-time tail iv streptozotocin (STZ, 35 mg/kg) was used to construct GDM model. The 50 rats successfully modeled were divided into model group, metformin group (Met group, 20 mg/kg), low NAR (NAR-L, 50 mg/kg), high (NAR-H, 100 mg/kg) dose groups and NAR+EX527 group (NAR 100 mg/kg+EX527 10 mg/kg), 10 rats per group. Rats in Met group and NAR low-dose and high-dose groups were given corresponding doses of drugs ig. Rats in NAR+EX527 group were given NAR ig and EX527 ip at the same time, once a day, for 28 consecutive days. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) in rats were detected, and the homeostasis model assessment for insulin resistance (HOMA-IR) was calculated; the levels of serum triglycerides (TG), cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were detected; the level of malondialdehyde (MDA) in pancreatic tissue and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected; the tissue lesions of pancreas and placenta were observed with HE staining; the expression of pancreatic tissue AMP-activated protein kinase (AMPK), p-AMPK, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1 α) proteins was detected with Western blotting method. Results:Compared with control, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the model group were significantly increased, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly reduced ( P<0.05), and the placenta and pancreas tissues showed obvious pathological damage; Compared with the model group, the FBG, FINS, HOMA-IR, serum TC, TG, LDL-C levels, and pancreatic tissue MDA level in the Met group and the NAR-L and NAR-H groups were significantly reduced, the SOD and GSH-Px activities, pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1 α expression levels were significantly increased ( P<0.05), the placenta and pancreas tissues damage reduced; and on the basis of NAR intervention, the use of SIRT1 inhibitor EX527 could significantly reverse the protective effect of NAR on GDM rats. Conclusion:NAR may improve glucose and lipid metabolism disorder and oxidative stress response in GDM rats by activatin SIRT1/PGC-1 α pathway.