| Objective: Vascular endothelial dysfunction is one of theinitial factor of atherosclerosis and its occurrence ordevelopment is related with insulin resistance (IR) closely. Asone of the chief endothelium-derived relaxing factors, nitricoxide (NO) production and dysfunction on regularizing vasculartone are important characteristic of endothelial cell damage andendothelial dysfunction. In this research, we fed male Wistarrats with high sucrose, high saturated fatty acid and highunsaturated fatty acid diets to observe the influence of thedifferent diets on IR and endothelium-dependent relaxationfunction, studying possible mechanism of vascular complicationin patients with type 2 diabetes mellitus (DM) and IR .Method: 56 adult, health,clean, male Wistar rats, 16~20weeks old, 250~300g weight, were purchased fromexperimental animal center in Hebei medical university andacclimatized for 2 week. Animals were randomly devided intonormal control (NC)group, high sucrose (HS) group, highsaturated fatty (HSF) group, high unsaturated fatty acid (HUF)group. NC group were fed regular diets which constitutes ofcalories from 65.5% for the carbohydrate, 10.3% for the fat,24.2% for the protein; high sucrose group were fed regular dietsmixed 20% sucrose, the carbohydrate provided 76.5% calorie,the fat provided 7% calorie, the protein provided 16.5% caloriein it; high saturated fatty group, high unsaturated fatty acidgroup were fed regular diets mixed 20% butter, 20% soybean,the carbohydrate provided 43% calorie, the fat provided 41%calorie, the protein provided 16% calorie in them. The sucrose,soybean oil, butter all came from experimental animal center inHebei medical university. Each proportion of unsaturated fattyacid and saturated fatty acids content is 84% and 16% in HUFgroup; the proportion of unsaturated fatty acid and saturatedfatty acids content is 69.1% and 30.9% in HSF group; puredegree of sucrose is 99%. Animals were fed 24 weeks. Bodyweight (BW), systolic blood pressure (SBP), fasting plasmaglucose (FPG), serum total cholesterol (TC), serum triglyceride(TG), fasting serum insulin (INS) were observed every 4 weekand serum free fatty acids (FFA), serum Nitric oxide (NO) wereobserved every 12 week during the 24-week feeding. IR wasevaluated by glucose infusion rate (GIR) of hyperinsulinemiceuglycemic clamp technique after 24 weeks.Acetylcholine-induced (or sodium nitroprusside-induced)relaxation of renal arteries were measured by isolated vascularrings detection technique, then vascular rings were incubatedwith L-arginine (L-Arg, substrate of NOS), Nω-nitro-L-arginine(L-NNA, inhibitor of NOS) and methylene blue (Mb, inhibitorof guanylyl cyclase) . Acetylcholine-induced relaxation of renalarteries were measured again.Result: 1. Body weight gain in HSF group, HUF groupincreased obviously, there were significantly difference thanthat of in NC group(p<0.05 or p<0.01)after 12 weeks, Bodyweight gain in HS group didn't increase obviously, showed nodifference between NC groups and HS group. At 24 week, Bodyweight in NC group,HS group,HSF group,HUF groupincreased 25.3%, 32.1%, 37.4%, 35.7% respectively. 2. Systolicblood pressure in experimental groups were higher significantlythan that of in normal control group(p<0.05), SBP went up inHSF group, HUF group , HS group fed after 4 week .The resultscontinued till 24 weeks. There were no difference amongexperimental groups. 3. FPG, TC, TG, INS in experimentalgroups all were much more than that in control group (p<0.05 orp<0.01), TC and TG in HSF group went up at the earlist stage,there were no difference among experimental groups at 24 week;FBG and INS in experimental groups were significantly higherin control group from 8 week(p<0.05 or p<0.01), there were nodifference among experimental groups. 4. FFA increasedsignificantly in 3 experimental groups compared with that in NCgroup after feeding for 12 week (p<0.01), FFA in HSF groupobviously higher than that in HS and HUF group (p<0.01), thesame results appeared at 24 week, but there were no differenceamong experimental groups. NO decreased significantly in 3experimental groups compared with that in NC group afterfeeding for 12 week (p<0.01), there were no difference amongexperimental groups, at 24 week, NO continued decreasing, NOin HSF group was the lowest than that in HS and HUF group(p<0.01). There were significant difference among them. 5. GIRwas obviously lower in experimental groups than that in NCgroup. From low to high, the consequence is HUF group, HSFgroup, HS group, NC group at 24 week. GIR in HUF group andHSF group is obviously lower than that in HS group(p<0.01 orp<0.01), GIR in HUF group is a little lower than in HSF groupbut there was no difference significantly. 6. Acetylcholine-induced endothelium-dependent relaxation were markedlydecreased in all experimental groups compared with the NCgroup (p<0.01) and the maximum relaxation were decreased37.4% in HSF group, 32.7% in HUF group, 27.7% in HSgroup. Sodium nitroprusside-induced endothelium-independentrelaxation showed no difference in 4 groups significantly. 7.Endothelium-dependent relaxation were enhanced incubatedwith L-Arg and decreased incubated with L-NNA and Mb in all4 groups, endothelium-dependent relaxation in normal controlgroup showed no difference among different incubation(p>0.05), endothelium-dependent relaxation in all experimentalgroups showed significantly difference incubated with L-Arg ,L-NNA and Mb(p<0.05 or p<0.01). 8. Endothelium-dependentmaximum relaxation was negatively correlated with BW, TG,INS, SBP and well positively correlated with NO, GIR. There...
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