Effects Of Rosiglitazone On Receptor For Advanced Glycation End Products (RAGE) In Liver Tissue Of Diabetic Rats

OBJECTIVE AND BACKGROUND:It is generally accepted that nonalcoholic fatty liver disease (NAFLD) is the most common liver disease of diabetes resulted, and NAFLD including four stages:simple fatty liver, steatohepatitis, hepatic fibrosis and cirrhosis. And the most characteristic lesion is nonalcoholic steatohepatitis (NASH). Insulin resistance (IR) plays an important role in the genesis and development of NAFLD. In hepatocytes, the insulin resistant state is brought about by at least one, but more likely by a combination, of the following pathological altercations: hyperglycaemia and hyperinsulinaemia, formation of AGEs, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. The engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory responses in various types of cells including hepatocytes and hepatic stellate cells. It has been reported that AGE levels in the liver from diabetic Chinese hamsters was significantly increased as compared with nondiabetic Chinese hamsters, and AGE staining was diffuse in the hepatocytes. And there was a significant increase in 1251-AGE binding in the liver of diabetic rats, also emulsion radioautography revealed that 1251-AGE binding was localised primarily in Kiipffer and liver endothelial cells. Liver is not only a target organ, but also an important site for clearance and catabolism of circulating AGEs. Rosiglitazone, one of thiazolidinediones (TZDs) compound, regarded as antidiabetic agent that improve insulin resistance and lipometabolism by acting as selective agonists of the nuclear peroxisome proliferator-activated receptor(PPAR)-γ. Recent studies have revealed that TZDs can block AGEs formation, anti-oxygenation and inhibit of the expression of RAGE mRNA in endothelial cells. However, there is few evidence to support the protective properties of diabetic liver disease through RAGE. In the present study, we investigated the expression of RAGE mRNA in diabetic liver tissue and whether rosiglitazone affects expression of RAGE in liver tissue of streptozotocin-induced diabetic rats.RESEARCH DESIGN AND METHODS:We induced Diabetic rats by an intraperitoneal injection of streptozotocin (STZ) in SD rats. The criterion of diagnosis of diabetes was the consecutive blood glucose level>16.7 mmol/L.27 male SD rats were randomly divided into 3 groups, Diabetes adding rosiglitazone group (DL group, intragastric administration rosiglitazone 5mg/kg.d) and Diabetes group (D group) and normal control group (C group). The body weight and blood glucose were measured every two weeks.8 weeks later, all rats were killed and the expression of RAGE was semiquantified in liver tissue by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:The RAGE expression was increased in liver tissue of diabetic rats. RAGE/β-actin ratio of diabetic group was significantly higher than that of the control (P<0.01),and after treatment of Rosiglitazone, RAGE expression decreased significantly (P<0.01). CONCLUSIONS:1. The high expression of RAGE may participate in the liver damage of diabetic rats.2. Rosiglitazone can protect the liver tissue from the impairment of hyperglycemia and AGE by decreaseing AGEs centents and inhibiting of the expression of RAGE mRNA in the liver.