Study On Block Cd40-cd40l Signal Occurrence In Diabetes Compliced Macroangiopathy Effect

Objective: The purpose of this study is to establish diabetes rats compliced macroangiopathy, after Simvastatin intervention, through detected serum soluble CD40 ligand, soluble Intercellular Adhesion Molecule-1,and CD40 ligand level in aorta pectoralis tissue, approach under hyperglycaemia and hyperlipemia condition Simvastatin block CD40-CD40L signal occurrence in diabetes compliced macroangiopathy effect.Methods: (1)use master single test intraperitoneal injection;peritoneal injection and vitamin D3 fractionation intragastric administration,fat animal feeds feeding to establish diabetes SD rats compliced macroangiopathy model,use blood sugar and aorta pectoralis common histomorphology inspection to evaluat this animal model success,to utilize enzyme linked immunosorbent assay to detect rat blood plasma sCD40L and sICAM-1 in protein level. Use immunohistochemistry technique to observe CD40L distribute in vascular lesion of aorta pectoralis and to compare histomogy absorption factor in different group rats.(2) grouping:common rat divide into normal hopylipoids contrast group(group A) eight,nomral Simvastatin intervention group(group B) eight,the form mode rats random to divide diabetic and macroangiopathy contrast group(group C)eighteen and diabetic and macroangiopathy Simvastatin intervention group(group D)sixteen.(3)medicine intervention:Simvastatin medicine suspension intragastric administration 8 week.(4)blood sugar determin adopt chemical method;blood plasma insulin adopt radio-immunity;blood fat adpot whole automatic detection;(5)To test the level of CD40L in tissue:when the experiment finished, sacrifice of all of animal, to abruptio aorta pectoralis immediately,use physiological saline to water flush,10 percent of formalin fixation after blot moisture content, common paraffin imbedding,then do immunohistochemistry,finish the dyeing,next apply image manipulation systems to measurement average optical.Results: (1) The model of diabetes compliced macroangiopathy rats appear persistent hyperglycaemia[groupA(4.32±1.08) mmol/l groupC(13.82±9.28)mmol/l],low insulin[groupA(21.21±8.47)uIU/ml groupC(9.94±3.48)uIU/ml],high cholesterol[groupA(4.06±0.85)mmol/l groupC(13.73±10.70)mmol/l],high triglyceride[groupA(0.36±0.09)mmol/l groupC(1.70±1.10)mmol/l];(2) histomorphology:groupA under the light microscope have no pathologic change;groupC aorta vessel wall thickening,smooth muscle cell proliferation and align anomalism,endothelial tissue and subendothelial layer have hydropic degeneration,the elastic fibrous layer structure is not clear,the part of vessel wallis inner outstanding,formed the fiber accrementition angiosclerosis'plaque; (3) the blood plasma sCD40L level:groupA(347.21±61.29)ng/ml groupC(1037.92±279.1)ng/ml;(4) the blood plasma sICAM-1 level:groupA(147.33±37.84)ng/ml groupC(203.38±76.72)ng/ml; (5) the CD40L absorbance value level in tissue:groupC(171.41±8.20)A groupA(98.63±12.50)A;in groupC,the CD40L level artery pathological changes endothelial cell and contractile fiber cells is higher than groupA's; (6)to compare the circa normal group,total cholesterol [groupA(4.06±0.85)mmol/l groupB(2.26±0.39)mmol/l],triglyceride[groupA(0.47±0.08)mmol/l groupB(0.36±0.09)mmol/l],low density lipoprotein[groupA(1.50±0.30) groupB(0.81±0.17)mmol/l],groupA and groupB aorta tissue not detected pathology change.(7)to compare the circa diabetic group,,total cholesterol [groupC(13.73±10.70)mmol/l groupD(4.33±1.52)mmol/l],triglyceride[groupC(1.70±1.10)mmol/l groupD(0.77±0.54)mmol/l],low density lipoprotein[groupC(5.51±5.04)mmol/l groupD(1.57±0.46)mmol/l];groupC aorta vessel wall thickening,smooth muscle cell proliferation and align anomalism,endothelial tissue and subendothelial layer have hydropic degeneration,the elastic fibrous layer structure is not clear,the part of vessel wallis inner outstanding,formed the fiber accrementition angiosclerosis'plaque;groupD rats'aorta vessel wall is also thickening,smooth muscle cell proliferation is lightener than groupC,endodermis and subendothelial layer hydropic degeneration is not obviously,is not observed obviously fibrous plaque. Conclusion: (1) use master single test intraperitoneal injection,peritoneal injection and vitamin D3 fractionation intragastric administration,fat animal feeds feeding can establish diabetes SD rats model.This model possess have the feature of type 2 diabetes glucose and fatty substance metabolism disordered, to have the characteristic of macroangiopathy pathological change. (2) diabetic macroangiopathy rats'aorta pectoralis tissue express CD40L,CD40L in part of vascular lesion endothelial cell and inflammatory cell have powerful mass concentration color. (3) Simvastatin can amelioration ipid metabolism disorder, restrain express the CD40L level in rat aortic tissue of diabetic macroangiopathy, maybe this is one of mechanism of it's antimacroangiopathy of diabetes.