Expression Of Sirt1 Mrna In Abdominal Aorta In Rats With Spontaneous Type 2 Diabetic Mellitus

ObjectivesType 2 diabetes mellitus is one of the major public health problems in the world, and its major complication,diabetic atherosclerosis, accounts for the leading death of diabetic patients. However, the underlying mechanism of diabetic atherosclerosis has not been fully clarified. SIRT1 is a NAD+-dependent deacetylase, which regulates life span in multiple model organisms in response to caloric restriction and has gained considerable attention for their relation with aging, diabetes mellitus, and atherosclerosis. In addition, recent studies point to SIRT1 as a key regulator of vascular homeostasis, whether SIRT1 play a role in the occurrence and development of diabetic atherosclerosis is not clear. Here, the expressions of SIRT1 in abdominal aorta of spontaneous diabetic rats were analyzed, and the effects of metformin on SIRT1 expression of abdominal aorta were also investigated.Contents1. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used. It develops diabetics spontaneously. The control is the nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. The morphology and structures of abdominal aorta of the OLETF and the LETO rats were compared.2. The expression of SIRT1 in the abdominal aorta of the OLETF rats and its effects on the development of diabetic atherosclerosis were studied3. OLETF rats were fed with metformin for 12 weeks and pathological changes in the abdominal aorta and SIRT1 expression were analyzed and compared with those of the rats fed with placebo.Methods1. mRNA levels of SIRT1 in abdominal aorta of LETO and OLETF rats were assessed by real-time PCR. The morphology of abdominal aorta of each group was observed by light microscope after HE staining.2. SPSS 16.0 software was used for statistical analysis. Comparison of numerical variable data was made with the single factor analysis of variance (ANOVA). Differences among individual groups were analyzed by SNK-q test.They were considered statistically significant when P<0.05.Results1. The expression of SIRT1 mRNA in the diabetic OLETF group was significantly lower than that in the nondiabetic LETO group (P< 0.05). Metformin treatment for 12 weeks significantly increased the levels of SIRT1 expression (P<0.05).2. Observations under light microscope revealed that, the intima was smooth without eminence and the smooth vascular cells in the tunical media were lining up in order in the abdominal aorta of the LETO rats;. But in the OLETF rats, the subendothelial space was widen, with less coloration and with a more loose configuration, suggesting fat deposition. Smooth vascular cells in the tunical media of the OLETF rats were deranged, suggesting their proliferation and migration into the intima. All the abnormal manifestations observed in the OLETF rats were consistent with early signs of atherosclerosis.Conclusions1. The lower expression of SIRT1 in the diabetic group is correlated with the occurrence and development of diabetes and its macrovascular compl' ations.2. Metformin treatment for 12 weeks greatly increased the levels of SIRT1 expression and improved atherosclerosis of the diabetic rats, which may be SIRT1-dependent.3. In conclusion, SIRT1 holds great promise as a target in the treatment of diabetic macrovascular diseases such as atherosclerosis.