| Objective:Stroke is the primary cause of death in China.The best treatment of stroke is prevention, and is the treatment of risk factors . As one of the four variable risk factors, diabetes mellitus and macroangiopathy atherosclerosis(AS) play a important role in the occurrence and prognosis of stroke. The pathological mechanism about diabetes macroangiopathy is not very explicit. Chronic inflammation may contribut to the pathologenesis. Many studies suggested the activation of nuclear factor-kappa B(NF-κB) and the expression of intercellar adhesion molecule-1(ICAM-1) in the endothelial cells are involed in diabetes macroangiopathy. The treatment of all kinds of metabolic disorders following with diabetes become the major point of preventing or delaying diabetes atherosclerosis occurrence and advance. Minidiab(Glipizide), an sulfaurea drug. Excepting for the definite role of reducing blood glucose, it has may exerts effects outside of pancreas,such as increases insulin sensitivity of outside tissue,regulating blood-lipid metablic disorders,inhibiting platelet clustering and so on. Simvastatin is regarded as the only drug that can stabilize and prevent the development of AS. It not only regulats blood-lipid but also has notregulating lipid effects: for example recovering endothelium function, resisting inflammation, inhibiting oxidization and influencing platelet function. Although it's molecular mechanism is not very understanded. In present study, we establish a rat modes of type 2 diabetes mellitus by feeding high sugar and fat diet to inducing insulin resistance and subsequently injecting small dose streptozotocin (STZ). And investigated early macroangiopathy of and the expression of NF-κB and ICAM-1 in vascular wall. At the same time rats are fed on minidiab and simvastatin to explore their molecule mechanisms and clinical practical values in the prevention and treatment of diabetes macroangiopathy. Methods: Female Wister rats were randomly assigned into two groups: normal control group(A) and diabetic making group(B). group A was fed with the normal diet, group B was fed with the high sugar and fat diets including sucrose(20%,w/w) and lard (15%,w/w) for 4 weeks to induce insulin resistance. Then hyperglycemia was developed by intrapenitoneal injection STZ (30mg/kg)in these rats. At 8 weeks diabetic rats were defined according to FBG more than average value added 3 standard error and reducing insulin sensitive index(ISI). Diabetic rats were randomly devided into three groups: diabetic group(DM),diabetic group treated with Minidiab (5mg/kg.d) (DG) and diabetic group treated with Minidiab (5mg/kg.d) and Simvastatin (2.5mg/kg.d) (DS). Body weight , fasting blood glucose (FBG) , fasting serum insulin (FINs) , serum triglyceride (TG) and serum cholesterol (TC) , low density lipidcholestrol (LDL-C) and high density lipid (HDL-C) were measured respectively after 4, 8 and 20 weeks. At the end of this study(20weeks), all rats were anesthetized by pentothal sodium(1%,w/w). Arotic tissues were revoved and were observed by light microscopy through hematoxylin-eosin stain(HE stain) and immuohischemisty statin of NF-κB and ICAM-1. Results:(1)In group B, fed with high sucrose and fat diet for 4 weeks, and body weight both were higher than group A(P<0.01, P<0.05); FINs,TC,TG and LDL-C significant increased levels(all P<0.01); ISI was lower (both P<0.01); But HDL-C was not clearly change. These results suggest insulin resistance in group B. (2) After injected a low dose of STZ intrapenitoneally for 4 weeks, group B rat's FBG markedly increased compared with group A(P<0.01); FINs,TC,TG and LDL-C were still higher and ISI continued to reduce(P<0.01). (3)After 20 weeks, compared with DM there were significant decreases in FBG(P<0.01) in DG; FINs and ISI both increased(both P<0.01); TC decreased but still was higher than DS(P<0.01), others elements of blood lipid didn't change obviously in DG(P>0.05). Compared with DM, there were obvious improvement of all indexs in DS (P<0.01). TC,TG,LDL-C and FINs were all lower in DS than DG (P<0.01). At that time, HDL-C and ISI both increased in DS (P<0.01). (4)Light microscopy results: aortic intima was smooth ,endothelial cells were flat and internal elastic membrane wassmooth in group A; Aortic intima was thickened, vascular smooth muscle cells were grown,endothelial cells were swelled and fell, internal elastic membrane was destroyed in DM, whlie pathological changs in DG and DS were abated significantly, and more significant in DS than DG (P<0.05). Immunohistochemical stain display that there are not expression of NF-κB and ICAM-1 in normal group. And there are positive expression of them in group DM,DG and DS. But NF-κB activation and ICAM-1 expression in group DG and DS are obviously lower than group DM (both P<0.01), and more obviously lower in DS than DG(P<0.05). [Integra optical density (IOD) indicats the degree of NF-κB activation and ICAM-1 expression.] Conclusions:(1)We successfuly establish the rat model of type 2 diabetes mellitus by fed with high sucrose and fat diet for 4 weeks, rats were injected a low dose of STZ intrapenitoneally. This model accompanied with hyperglycemia, hyperlipid, hyperinsulinmia and insulin resistance is similar to type 2 diabetes of human. It is used to study the molecule mechanism and the drug treatment of chronic complications of type 2 diabetes mellitus in human. (2) NF-κB activation and ICAM-1 expressions are both significant increased in aortic tissue of type 2 diabetes. These results that inflammatory reaction involed NF-κB activation occurred in artery walls of early stage of DM, and ICAM-1 also increase. The progress of AS is switched on by these major segments. It suggests blocking this segment in... |
PDF Full Text Request