大鼠肝脏组织蛋白磷酸酶2A z-bo 2020-11-12 352

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

　　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); the control group (n=20) was given the same amount of normal saline by gavage on an empty stomach every day, and the weight and fasting blood glucose of the rats were measured monthly. After 5 months, the rats were sacrificed, and blood was collected by cardiac puncture, pancreatic tissue and liver tissue were collected, and the serum insulin level of the rats was measured. The histopathological observation of the pancreas was performed. The liver tissue processing and immunohistochemistry were performed to detect the 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 rats was significantly increased, and the expression of phosphorylated AKT was significantly decreased.

　　Conclusion: Tacrolimus causes pancreatic islet cell necrosis, decreases the number of pancreatic 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.