|
Objective Vascular lesion is result in all kinds of diabetic chronic complication in the final analysis.The macroangiopathy is the main dead reason of type 2 diabetes mellitus （T2DM）.Vascular endothelial dysfunction is considered of the premise of diabetic vascular lesion,and it also play an important role in the development in the atherosclerotic.Thiazolidinediones（TZDs） could depress blood glucose,impro（?）e insulin resistance,retrieve metabolic symptom complex,resist oxidative stress,（?）gainst inflammatory reaction,depress blood pression and ameliorate vascular endoth（?）l dysfunction.The objective of this researth is to observe effects of pioglitazone the vessel and endothelial function,the ultramicrostructure and inflammatory fac（?） of rat models with type 2 diabetes accompanying insulin resistance;To observe the vasomotion effect of PIO on Sprague-Dawlay rat thoracic aorta rings and the ur（?）-rlying mechanism were investigated.Methods①52 male SD rats were separated into 2 groups randomly:normal con（?） group（n=18）,and the others were fed with high-fat emulsion via gavage for 5 months, insulin sensitivity were evaluated using euglycemic hyperinsulinemic clamps technique by observeing their glucose infusion rate.Streptozotocin and complete Freund’s adjuvant were administered to the remain rats via intraperitoneal injecting,to establish the rat model with T2DM accompanying insulin resistance.Rats with type 2 diabetes were separated into DM and PIO group randomly,the PIO group were administed pioglitzone via gavage（10mg/kg.d）.After 6 weeks,body mass,heart mass /body mass, systolic blood pressure、fasting blood glucose,glycosylated hemoglobin-A1c, C-reactive protein,CRP、nitric oxide,endothelin and fasting insulin were measured and artedae aorta,vessel endothelium cells samples were observed using light microscope and electron microscope respectively.②To execute the rat by ceruical uertebra dislocation,and to dissociate thoracic aorta immediately,the thoracic aorta was cut into thoracic aorta rings about 2mm,to establish a rat exvivo thoracic aorta rings perfusion model.SD rats were separated into NC and PIO group randomly,the PIO group was added into organ bath in different density（3μmol/L、10μmol/L、30μmol/L） one by one.To observe the effect of PIO on the endothelium intact thoracic aorta rings.Results①After the treatment,compared with the NC group,the SBP,surcm FBG, HbA1c in the DM group increased,there was significant difference（P＜0.05）, compared with the DM group,FBG,HbA1c,Fins in the PIO group decreased,there was significant difference（P＜0.05 ）,there was no significant difference in SBP between DM and PIO groups（P＞0.05）.②The level of serum CRP in the DM group were significantly higher than those in the NC and PIO groups（P＜0.05 ）,and there was no significant difference between the NC and PIO groups（P＞0.05）.③The level of serum NO in the DM and PIO groups were significantly lower than those in the NC group（P＜0.05）,the level of serum ET in the DM and PIO groups were significant higher than those in the NC group（P＜0.05）,compared with the DM group,the NO in the DM group increased,there was significant difference（P＜0.05 ）,there was no significant difference in the level ofsurum ET between the DM and PIO groups（P＞0.05 ）.④Compared with NC group,the level of FIns increased,insulin sensitivity index（ISI） decreased,homeostasis model asessment-insulin resistant index（HOMA-IR） increased in DM group,there was significant difference（P＜0.05 ）;compared with DM group, Fins decreased,ISI increased,HOMA-IR decreased in PIO group,there was significant difference（P＜0.05）.⑤Compared with DM group,there existed a significant improvement of the arteriae aorta ultramicrostructure in the PIO group.⑥Compared with NC group,different density of PIO induced the grounding tension decreasing in the endothelium intact rings,there was significant difference（P＜0.05）.⑦PIO at low concentration（3μmol/L） induced vasodilation,exposure of endothelium intact rings to PIO at low concentration（3-10μmol/L） induced a significant concentration dependent relaxation.When the density accumulated to 30μmol/L,the vasodilation did not increase no longer.Conclusion①PIO improved insulin resistance in the rats with T2DM,and decreased the level of FBG and HbA1c.②PIO improved the morphologic lesioning of arteriae aorta and vessel endothelium cells in the rats with T2DM.③PIO improved blood vessel endothelium dysfunction.④Inhibiting inflammatory reaction may be one of the mechanism for vessel and endothelium procection of PIO.⑤PIO at low concentration induced a significant relaxation on the rat exvivo thoracic aorta rings,and there was dose-dependent effects of relaxation in a certain extent of density.
|