Relationship Between Macroangiopathy And Related Factors Of Insulin Resistance In Rat Model Of Type 2 Diabetes Mellitus And Drugs Treatment

Objective:Macroangiopathy is one of the majorcomplications of type 2 diabetes mellitus.Its basic pathologicphysiology phenomenon is atherosclerosis. The pathophysio-logical mechanism of atherosclerosis has not been explainedexactly, but insulin resistance and the abnormal metablismlinked to insulin resistance are the risk factors of atherosclerosis.Rosiglitazone belongs to thiazolidinediones (TZDs), a kind ofnovel insulin sensitizer,and plays important roles in improvinginsulin resistance and reducing serum insulin level andinhibiting the development of atherosclerosis. Metformin notonly can reduce hyperglycemia by increasing glucose intakingand inhibiting glyconeogenesis and glycogenolysis, but alsoplays significant part in decreasing hyperlipemia andhypertension and in improving hemodynamic changs and thediastolic function of vascular smooth muscles, which isbeneficial to diabetic macrovascular. Therefore, in this studyrats model of type 2 diabetic was set up by feeding female SDrats with a high-sucrose-high-fat diet and by injecting themstreptozotin intrapenitoneally. Rosiglitazone and metforminwere given to type 2 diabetic rats after 8 weeks. On thiscondition, to observe the abnormal metabolism linked to insulin──────────────────────────────────────── 6英 文 摘 要resistance and investigate the pathophysiological mechanism ofdiabetic macrovascular complication. Morever, roles ofrosiglitazone and metformin are made clear in inhibiting thedevelopment of atherosclerosis. Methods:Female SD rats were randomly assigned into twogroups: normal control group(NC) and diabetic group(DM).Normal control group was fed with the normal diet, whilediabetic group was fed with the diets enriched withsucrose(10%,w/w) and lard(15%,w/w)and cholesterol(2%,w/w)and cholic acid(0.25%,w/w) to induce insulin resistance.Hyperglycemia was developed by intrapenitoneal injection STZ(30mg/kg)in these rats after 4 weeks on this diets . At 8 weeksdiabetic rats were randomly devided into three groups: diabeticcontrol group (DC) ,diabetic group treated with rosiglitazone(3mg/kg.d) (DR) and diabetic group treated with metformin(625mg/kg.d) (DM). Body weight, fasting blood glucose, fastingserum insulin, serum triglyceride and serum cholestrol weremeasured respectively after 4, 8 and 18weeks. Serum tumornecrosis factor- alpha, serum leptin and urinary albuminexcretion rate (UAER) were respectively observed after 18weeks.The protein expression of tumor necrosis factor- alphawas examined by immuohischemisty. The aortic tissue wasobserved by light microscopy. Morever, the correlation betweenthe factors linked to insulin resistance and insulin sensitivityindex and the size of aortic injure were respectively analyzed. Results:(1)In diabetic group, fed with high-sucrose-high──────────────────────────────────────── 7英 文 摘 要-fat diet for 4 weeks, body weight was markedly increasedcompared with normal control group (P<0.01); serumtriglyceride, serum cholestrol and serum insulin level wereincreased compared with normal control group (P<0.05, P<0.05,P<0.01); fasting blood glucose had no difference with normalcontrol group (P>0.05); ISI was markedly decreased comparedwith normal control group (P<0.01).So insulin resistance wasinduced in diabetic group . (2) After diabetic group was injecteda low dose of STZ intrapenitoneally, at 8 weeks fasting bloodglucose level was markedly increased compared with normalcontrol group (P<0.01),and serum insulin level was decreasedcompared with 4 weeks before, but had no difference withnormal control group (P>0.05); ISI was markedly decreasedcompared with normal control group (P<0.01).So insulinresistance still existed in diabetic group . Body weight wasincreased compared with normal control group, but no markedlysignific...