Abstract: Objective To observe the therapeutic effect of saxagliptin in a rat model of nonalcoholic fatty liver and type 2
diabetes and investigate the possible mechanism. Methods Rats models of nonalcoholic fatty liver and type 2 diabetes
established by feeding on a high glucose and fat diet and streptozotocin injection were treated with saxagliptin (daily dose of
10 mg/kg) gavage for 8 weeks, using saline as the control. After the treatment, fasting blood glucose, serum insulin, blood
lipids, liver function, liver oxidative indices, and hepatic pathologies were evaluated in all the rats, and the expressions of Bcl-2
and Bax in the liver tissue were detected with immunohistochemistry and Western blotting. Results Compared with the model
group, saxagliptin intervention significantly reduced blood glucose and HOMA-IR, improved the liver function and SOD
activity (P<0.01), lowered the liver weight, liver index (P<0.01) and MDA level (P<0.05), and slightly lowered the body weight
and blood lipids (P>0.05); AST level was similar between the normal control group and saxagliptin intervention group (P>
0.05). HE and oil red staining showed obvious hepatic pathologies in the model group, and saxagliptin intervention
significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver. Hepatic Bax
expression significantly increased and Bcl-2 expression decreased in the model group, and these changes were reversed by
saxagliptin. Conclusion Saxagliptin shows good therapeutic effect in rat models of nonalcoholic fatty liver and type 2 diabetes
possibly by controlling blood glucose, lowering insulin resistance, alleviating hepatic oxidative stress and hepatocyte damage,
and regulating the expression of apoptosis-related proteins.