ABSTRACT
AIM:To investigate the effect of irbesartan on the fatty liver of db/db mice and whether autophagy is involved in the process.METHODS:Male db/db mice(n=24)were randomly divided into model group and irbesar-tan group,and 12 db/m mice with similar age and weight were selected as normal control group.After 16 weeks of inter-vention respectively,the fatty liver-related parameters including body weight, liver index, blood lipid, liver function and pathological changes in the liver were observed.The protein levels of p-PI3K,p-Akt,and p-mTOR,as well as Atg-7,bec-lin-1 and LC3B in the liver tissues were detected by Western blot,and the autophagosomes in the liver were observed under electron microscope.RESULTS:Compared with the model group,the body weight,liver index,blood lipids,alanine and aspartate aminotransferase were decreased in irbesartan group(P<0.05).Moreover,the pathological changes in the liver were significantly ameliorated in irbesartan group than that of model group.Importantly, the protein levels of p-PI3K, p-Akt and p-mTOR were decreased with irbesartan administration,while the expression of Atg-7,beclin-1 and LC3B-Ⅱwas increased(P<0.05),which resulted in a distinct increase in autophagosomes.CONCLUSION:Irbesartan alleviates he-patic steatosis in db/db mice by inhibiting the PI3K/Akt/mTOR signaling pathway and upregulating the protein expression of Atg-7,beclin-1 and LC3B-Ⅱ,thereby inducing autophagy in hepatocytes.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms.</p><p><b>METHODS</b>Twenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IκBα ,IκBα and β-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-α mRNA were detected using quantitative real-time PCR (qPCR).</p><p><b>RESULTS</b>Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IαBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-α in the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice.</p><p><b>CONCLUSION</b>Treatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin II and NF-κB signaling pathway.</p>