The Mechanism Of Adhesion Molecule Production In Diabetic Microangiopathy And Effect Of Infervention

Recently the role of cell adhesion molecule in diabetic chronic complications(DCC) is increasingly recognized. Vascular cell. adhesion molecule-i (VCAM- 1) is an important member of immunoglobulin super family. VCAM-l has been found to be involved in many pathophysiological processes, such as inflammatory reaction, inimunoloregulation, blood coagulation and thrombosis formation,etc. Diabetic angiopathy, especially microangiopathy, is the congenerous pathological bottom and core link of DCC. However microangiopathy always occurs earlier and more extensive. In this study the microvascular endothelial cells cultured in vitro and the patients with diabetes mellitus(DM) act as the investigation objects, and the purpose of this study is to observe the role of VCAM-1 in diabetic microangiopathy. Content: Observe the effect of high concerntration glucose on VCAM-1 expression on microvascular endothelial cells cultured in vitro. Observe the effect of advanced glycosylation end products(AGE5) on VCAM-1 expression on microvascular endothelial cells cultured in vitro.Investgiate the effect of some drugs and Chinese herbs on AGEs formation and on VCAM-l expression on microvascular endothelial cells in vitro stimulated by AGEs. Determine the level of TNF a of the cultured medium to find the correlation between TNF a level and VCAM-1 expression. Determine the change of serum sVCAM-1 and TNF a in patients with DM to assay the clinical significance. Observe the change of these parameters after vitamin nutrien intervention on patients with type 2 DM and discuss the role and significance of the nutrien intervention. Observe the change of these parameters on patients with type 2 DM after pioglitazonetreatChnt, discuss the ro1e of pioglitazone and analyze its clinical significance.MethodWe stUdy by both cel1 cultUred in vitro and stUdied in vivo, anmal exPerimentand clinical investigation. Microvascular endothelial cells cultUre model in vitro,inununohistochemistry ABC, flow cytometer assay, radio-iInmtalty analysis,enZyme-linked inuntmsorbent assay and drug interventon are also used..Re8ults:l. Effects of high concemtration glucose and AGEs on VCAM-l expression onmouse heat microvascular endothelial cells: l2mM. 20mM glucose and AGEs(l00ug/ml. 200ug/ml. 400ug/ml) could increase the expression of VCAM-l onMHMEC, compared with the basal leve1. BetWeen the l2tnM and 20mM glucosegrOuP, there was extTaordinary significat difference. 20rnM glucose and AGEs hadsynergistic action.20mM glucose and AGEs combined stimulation could increase theexPression of VCAM-1 on MHMEC more over, compared with stimuation alonethere was significat difference.2. Effects of some drugs on AGEs stimulated VCAM-l exPression on MHMEC:Quercetin. probucol. N-acetylcysteine could inhibit the exPression on MHMECdoseage-dePendently Stimulated by AGEs: VitaminE. VtarninC could also inhibit theexpression on MHMEC stimulated by AGEs and had synergistic action;aminoguanidin could not inhibit the expression on MHMEC induced by AGEs.3. The change of ThF Q leve1s in MHMEC cultured medium: the level of ThFacultUred with 20mM glucose \ AGEs increased significatly. There wasextraordinary significant difference compared with the control groop, the level ofTNFa cu1tUred with 20tnM glucose combined AGEs increased more over, comParedwith 20rnM glucose \ AGEs cultUred alone, there was sighfican difference. Thelevel of mFa colbed with quercetin. probuco1. N-acetylcySteine significatlydecreased compared with the positive control (AGEs stimulated), there wassignifican difference. There was no significant difference betWen the levels ofTN'Fa colthed with vitaminE. vitaminC alone or combined.4. The change of serum sVCAM-l. mF Q...