Abstract: Abstract: Objective　To investigate the therapeutic effect of irbesartan on fatty liver in diabetes-hypertension (SHDM) rats and its influence on the AMPK/mTOR signaling pathway mediated by peroxisome proliferator-activated receptor γ (PPAR-γ). Methods　The rat model of SHDM was induced by intraperitoneal injection of streptozotocin with high fat high sugar diet in spontaneously hypertensive rats. SHDM model rats were randomly divided into model group, irbesartan group and irbesartan + PPAR-γ antagonist group. In addition, the normal rats were used as the normal control group. After 8 weeks of intervention, the changes of blood pressure, blood glucose, blood lipid, liver function and liver pathology were observed. The expression levels of PPAR-γ, AMPK/mTOR pathway molecules and LC3B in liver tissues were detected by Western blot assay, and the autophagosomes in the liver were observed under electron microscope. Results　Compared with the model group, the systolic blood pressure, blood glucose, blood lipid, liver function and liver pathology were significantly ameliorated in irbesartan group (P＜0.05). However, the above indexes except for the blood glucose were all increased after treatment with irbesartan and PPAR-γ inhibitor. Importantly, the protein levels of PPAR-γ, p-AMPK and the LC3B Ⅱ/Ⅰratio were increased with irbesartan administration, while the expression of p-mTOR was decreased (P＜0.05), which resulted in a distinct increase in LC3B Ⅱ/Ⅰratio and autophagosomes. There were significant differences in these indicators between model group and irbesartan group (P＜0.05). However, these effects were reversed after treatment with irbesartan and PPAR-γ inhibitor treatment. Conclusion　Irbesartan has a therapeutic effect on fatty liver in SHDM rats, and its mechanism is related to the activation of PPAR-mediated AMPK/mTOR pathway, thereby promoting hepatocyte autophagy.

Key words: hypertension, diabetes mellitus, fatty liver, PPAR gamma, AMP-activated protein kinases, TOR serine-threonine kinases, autophagy, Irbesartan