动物造模 z-bio 2022-07-27 549

　　Objective: By observing the effects of tacrolimus on blood glucose, insulin levels, hepatic tissue protein phosphatase 2A and phosphorylated AKT expression in rats, to further explore the mechanism of tacrolimus-induced blood glucose elevation.

　　Methods: 60 male SD rats (89.83±4.44) g were randomly divided into two groups, the tacrolimus group (n=40), and the daily fasting (fasting water 8 h) intragastric administration, the dose of 4 mg/(kg·d); in the control group (n=20), the rats were given the same amount of normal saline by gavage on an empty stomach every day, and the body weight and fasting blood glucose of the rats were measured monthly. After 5 months, the rats were sacrificed, blood was collected by cardiac puncture, pancreatic tissue and liver tissue were collected, serum insulin levels were measured, pancreas histopathological observation was performed, and liver tissue processing and immunohistochemical techniques were used to detect the content of liver cytoplasm. Expression of protein phosphatase 2A and phosphorylated AKT.

　　Results: After 2 months of treatment, the blood glucose level of the rats in the tacrolimus group was significantly higher than that in the control group (P < 0.05), and the insulin secretion index and insulin sensitivity index of the rats in the tacrolimus group were significantly lower than those in the control group. (P < 0.05); the insulin resistance index was significantly increased (P < 0.05). Compared with the control group, the expression of PP2A in the cytoplasm of the tacrolimus group was significantly increased, and the expression of phosphorylated AKT was significantly decreased.

　　Conclusion: Tacrolimus leads to islet cell necrosis, decreased islet cell number, decreased insulin secretion, decreased insulin sensitivity, and increased insulin resistance, resulting in increased blood sugar in rats. Tacrolimus increased the expression of PP2A in rat liver tissue and decreased the expression of phosphorylated AKT in liver tissue, which may be involved in islet cell apoptosis and insulin resistance through the PI3K/AKT signal transduction pathway, resulting in the increase of blood sugar.