动物造模 z-bio 2022-01-14 374

　　Objective: To further explore the mechanism of tacrolimus on blood glucose, insulin level, liver tissue protein phosphatase 2A and phosphorylated AKT expression in rats by observing tacrolimus.

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

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

　　Conclusion: Tacrolimus causes islet cell necrosis, decreases the number of islet cells, decreases insulin secretion, decreases insulin sensitivity, and increases insulin resistance, which leads to increased blood sugar in rats. Tacrolimus increases the expression of PP2A in rat liver tissues and reduces the expression of phosphorylated AKT in liver tissues. It may participate in islet cell apoptosis and insulin resistance through the PI3K/AKT signal transduction pathway, causing an increase in blood sugar.