Expression Of S100B In Diabetic Rat Aorta And Effect Of Irbesartan On Expression Of S100B

Background and Objective Accelerated and aggressive atherosclerosis is the major cause of morbidity and mortality in patients with diabetes. Previous studies suggested that receptor for advanced glycation end products (RAGE) contributed to lesion progression in atherosclerosis. Its proinflammatory ligands, advanced glycation end products (AGEs) and S100/calgranulins in vascular perturbation, manifested as enhanced atherogenesis. S100/calgranulins are predominately intracellular calcium-binding proteins which contain two EF hand regions. We proposed that activation of RAGE by S100B would induce a sustained inflammatory response and oxidant stress, and causes increased vascular permeability, expression of cell adhesion molecules, such as vascular cell adhesion molecule-1, nuclear translocation of NF-κB. Irbesartan, a specific angiotensin ⅡsubtypeⅠreceptor antagonist, can inhibit formation and development of atherosclerosis. We have known that irbesartan decrease the cytoplasmic Ca2+ concentration, inhibit the proliferation of vascular smooth muscle cells. Up to date the mechanism of irbesartan antiatherosclerosis is not clear. to investigate its antiatherosclerotic mechanism.AIM: To observe the expression of the S100B and the effect of irbesartan on expression of aortic S100B in streptozotocin-induced diabetic rats. METHODS: SD rats (n = 120) were randomly assigned to three groups: control group (CON, n=40), Diabetic group (DM, n=40), Irbesartan group (DMI, n=40). The rats of each group again were randomly assigned to four subgroups by intervention time: one group for 1 week (n=10), one group for 2 weeks(n=10), one group for 4 weeks (n=10), one group for 8 weeks (n=10). S100B mRNA and protein were determined by semi-quantitative RT-PCR and immunohistochemistry.RESULES: Compared with nondiabetic aortas, diabetic aortas is increased the level of mRNA and protein of S100B (P<0.001). The expression S100B by irbesartan therapy is partly reduced (P<0.05), but still high than those of control group (P>.05).CONCLUTIONS: 1.These results indicate that the expression of the S100B is elevated in diabetic rat. It is suggested that members of the S100/calgranulin family may, along with AGEs, mediate inflammatory responses that trigger cellular activation and dysfunction in diabetic tissue. 2. Irbesartan could reduce the atherosclerosis progress by inhibiting the expression of the S100B in diabetic rats.