Effects of Zuogui Jiangtang Jieyu Formulation on insulin resistance in hipppocampus of rats with diabetes-related depression / 中草药

ABSTRACT

Objective: To investigate the function of Zuogui Jiangtang Jieyu Formulation on hippocampal insulin resistance in rats with diabetes-related depression. Methods: The rat model of diabetes-related depression was established and randomly divided into four groups, including model group, positive drug group (metformin 0.18 g/kg + fluoxetine 1.8 mg/kg), high (20.53 g/kg) and low (10.26 g/kg) doses of Zuogui Jiangtang Jieyu Formulation groups. After 28 d of gavage, fasting blood glucose and peripheral insulin resistance were measured by blood glucose meter and ELISA. The depression-like behaviors of rats were tested by open field experiment and forced swimming test. The expression of p-IR and p-IRS-1 in hippocampus of rats were detected by immunofluorescence and Western blotting, while the levels of p-PI3K and p-Akt were detected by Western blotting. Results: Compared with the normal group, the blood glucose of rats in model group were significantly increased, which accompanied by obvious peripheral insulin resistance. The number of activities in open field experiment was significantly reduced in model group, and the immobility time in forced swimming experiment was significantly prolonged. In addition, it was showed that the levels of p-IR, p-IRS-1, p-PI3K and p-Akt in the brain of model rats were all significantly decreased. Compared with the model group, the blood glucose and insulin levels were significantly decreased in high-dose of Zuogui Jiangtang Jieyu Formulation group. Furthermore, the depression-like behaviors manifested in open field experiment and forced swimming experiment were improves by high dose of Zuogui Jiangtang Jieyu Formulation. More importantly, the expression of p-IR, p-IRS-1, p-PI3K and p-Akt in hippocampus was significantly increased in high dose of Zuogui Jiangtang Jieyu Formulation group compared with model group. Conclusion: Zuogui Jiangtang Jieyu Formulation can effectively regulate the insulin signaling pathway in hippocampus of rats with diabetes-related depression, and then improve the insulin resistance in the brain of model rats.