【Animal modeling】-Intervention effect and mechanism of Exendin-4 on STZ-induced diabetic nephropathy in rats

  Objective To study the intervention effect and possible mechanism of Exendin-4 on streptozotocin-induced diabetic nephropathy in rats.

  Methods A total of 60 SD healthy rats with no specific pathogens were selected. A diabetic nephropathy rat model was established in 45 rats and randomly divided into model group, benazepril group, Exendin-4 low, medium and high dose groups, and blank group For healthy rats, there are 9 rats in each group. After successful modeling, the benazepril group was given 10 mg/kg benazepril tablets by gavage, the Exendin-4 low, medium and high dose groups were subcutaneously injected with Exendin-4 4, 20, 100 μg/kg, respectively, the normal group and The model group was given purified water by gavage. After 1 week of administration, the total cholesterol (TG), triglycerides (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (low-density lipoprotein cholesterol) were detected in each group. density lipoprotein cholesterol, LDL), amylase (amylase, AMY), blood glucose (blood glucose, BG), glycosylated hemoglobin (hemoglobin, HbAlc), fasting serum insulin (fasting serum insulin, FINS), body weight, renal index (renal index, RI), glomerular area, glomerular diameter, and protein expression of advanced glycation end products (AGEs), PDK1, p-Akt, and p-mTOR in renal tissue.

  Results The expressions of TG, TC, LDL, BG, HbAlc, FINS, AGEs, body weight, RI, glomerular area, glomerular diameter, PDK1, p-Akt, p-mTOR protein expression in Exendin-4 medium and high dose groups The amount of TG, TC, HDL, LDL, BG, HbAlc in the high-dose Exendin-4 group was significantly lower than that in the low-dose Exendin-4 group, and HDL was higher than that in the low-dose Exendin-4 group (P<0.05). , FINS, AGEs, RI, glomerular area, glomerular diameter, PDK1, p-Akt, p-mTOR protein expression were lower than those in the middle-dose Exendin-4 group, and HDL was higher than that in the middle-dose Exendin-4 group. There were significant differences in TC, HDL, LDL, AMY, HDL, body weight, RI, and glomerular area (P<0.05).

  Conclusion Exendin-4 can reduce the level of inflammation in STZ-induced diabetic nephropathy rats, improve their BG, blood lipids and pancreatic function, and its mechanism may be related to the inhibition of PDK1/Akt/mTOR pathway. This study provides a new direction for the clinical treatment of other inflammatory conditions such as diabetic nephropathy.