| Objective To make diabetic rat vascular stenosis model.To explore the neointimal formation, the proliferation of vascular smooth muscle cells (VSMC) in neointima, the deposition of advanced glycation end products (AGE) and the expression of receptor for AGE (RAGE) in vascular wall in diabetic Wister rats after carotid artery balloon injury. To investigate the effects of aminoguanidine (AG) on the neointimal formation and to supply the theoretic evidence of for prevention and treatment of restenosis after angioplasty.Methods One hundred and twenty healthy male Wistar rat, 200~275g weight, after 1 week's observe, were injected into celiac with 0.1mmol/L STZ (60mg/kg, soluted with citriac sodium buffer solution, pH4.2, 4℃). Rats whose blood glucose levels were above 16.7mmol/L were taken as diabetic rats after 72 h. The rats were randomly divided into two groups: diabetic group and AG group. AG 100mg/kg.d was injected into stomach in AG group, and equal capacity of NS injected into stomach in diabetic group. All rats were anesthesized with 3% pentobarbital sodium (25mg/kg). The distal left common carotid artery of all animals exposed through a midline wound in the neck. The left common carotid artery was denuded of endothelium by the intraluminal passage of 2 F balloon catheter introduced through the external carotid artery following a 0.014 inch guide wire. The balloon catheter was passed three times with the balloon dilated sufficiently with saline to generate slight resistence. The dilation of balloon also caused the expansion of the carotid itself. The externalcarotid was ligated after removel of the balloon catheter and the wound closed. The completeness of denudation was conformed by optical microscope and scanning electron microscopy on perfusion- fixed specimens. All survival rats (15 rats in diabetic group and 15 rats in AG group) were killed 4 weeks after the operation, and common carotid arteries and other samples needed were taken. Blood glucose, lipid, cholesterol, serum AGE and tissue AGE were measured. The area of neointima and vascular lumen were measured. The specimens of common carotid artery tissue was dyed by means of immunohistochemistry to detect AGE deposition and PCNA stained positive cells in injured artery wall. The specimens were perfusion-fixed for electron microscopy examination. Tissue total mRNA was abstracted from 50mg common carotid artery with Trizol reagent, and RT-PCR was performed to observe the expression of RAGE.Results The AGE levels were markedly increased in diabetic group than that in AG group (P<0.001). There were no significantly morphological changes in the uninjured common carotid artery between diabetic group and AG group. There were severe morphological injuries in the injured common carotid artery in both diabetic group and AM group after angioplasty immediately. The endothelium disappeared, and internal elastic plate was broken after injury. After 4 week, the endothelial cell was integrated partly and a large number of endoplasmic reticulum and Golgi complex and little myofilament in cytoplasm of VSMC were observed in two group. VSMC showed synthetic phenotype and the intima became thicker. The changes were more remarkable in diabetic group than that in AG group. When compared with diabetic group, the vascular lumen area were increased (PO.001), the area of neointima (PO.05), the AGE stained positive area (PO.001), the RAGE expression (PO.001), the amount of PCNA stained positive cells were decreased (PO.001) in AG group. The area of neointima was correlated with the serum AGE levels, carotid artery tissue AGE levels, the area of AGE deposition, the expression levels of RAGE and PCNA stained positive cells in injured artery wall.Conclusions ?The diabetic rat vascular stenosis model can successfully...
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