Effect of Fosfenpril and Telmisartan on ACE2Expression of Carotid Artery Intimal after Balloon Catheter Injury in a Model of Type2Diabetes Rat
|School||Chongqing Medical University|
|Keywords||type2diabetes rat angiotensin-converting enzyme2 angiotensin receptor blocker arterial intimal hyperplasia telmisartan|
Backgroud and object: Diabetes mellitus(DM) whichco-existed withdyslipidemia and hypertension usually，is one of the mostimportant healthproblems at present. The mechanisms of DM caused thedamage of majororgans was vascular injury. However, the mechanisms of vascular injury indiabetesmellitus is not clear，and need to find effective control methodsurgently.Telmisartan is the only angiotensin II receptor blocker(ARB)withselective PPARγ-modulating activity. It can improve insulin resistanceandreduce blood sugar levels. Angiotensin-converting enzyme inhibitors(ACEI), is proven to be effective in apoptosis inhibition and in improvingventricular remodeling. Angiotensin-converting enzyme2(ACE2) is a newfound enzyme which is the homologue of ACE,ACE2may plays aprotective role to the Vascular, RAS and ACE2may influence each other.But few researchs had been done to observe the change of ACE2afterintimal were detected by Immunoblot, so as to the impact of RAS inhibitorson it. The combination of ARB and ACEI in the treatment of diabetic endothelial injury and its mechanisms, is waiting for being illuminated. Inour study, we treated diabetic rats by administration of single telmisartan,single fosinopril and the combination of fosinopril and telmisartan aftercarotid artery balloon injury, observed the effects on expression of ACE2inthe carotid artery intima after balloon catheter injury,and the change ofintimal hyperplasia after drug intervention preliminary,investigate theirpotential mechanisms in preventing endothelial injury and to providexperimental proof for searching more effective treatment of diabeticmacroangiopathy and resenosis after PTCA in clinical work.Methods: Six of the36healthy male Sprague-Dawley rats were asrandomly selected normal group(n=6),other30rats were used to establishmodel of diabetes. Six of the modeling diabetic rats were drawn outrandomly as Diabetic control group and the others were randomly dividedinto4groups balloon injury alone group (balloon injury plus saline; n=6);telmisartan group (balloon injury+telmisartan0.8mg/kg.d;n=6); fosinoprilgroup (balloon injury+fosinopril10mg/kg.d; n=6); and combination group(balloon injury+telmisartan0.8mg/kg.d+fosinopril10mg/kg.d;n=6). All ofthe rats were examinated fasting blood glucose,blood lipids,insulin of tailsblood and measured blood pressure, heart rate, body weight; ACE2mRNAwere measured by Reverse Transcriptase Polymerase Chain Reaction(RT-RCR). angiotensin-converting enzyme2(ACE2) protein expression ofintimal were detected by immunohistochemistry. Results:(1) Compared with normal group:the systolic blood pressure(SBP) of diabetic group was no significant difference (P>0.05)；(2) bloodlipids, serum insulin (FNS) was significantly increased(P<0.01);(3)Compared with the normal SD rats, carotid ACE2mRNA and proteinexpression were significantly decreased in balloon injury alone grouprespectively. With balloon injury alone group, Telmisartan group caused asignificant increase in ACE2mRNA expression, fosinopril group had nosignificant differences in the ACE2mRNA and protein expression.Conclusions:(1) We can replicate the model of type2diabetes by feedingfat-rich and glucose-rich diet combined with intraperitoneal injection lowdose STZ;rat carotid artery balloon injury model which can stimulatediabetic macrovascular intimal hyperplasia is a ideal model to study themechanism of neointimal formation and determine the anti-proliferativeeffect of drugs (2) intima decreased levels of ACE2expression in diabeticrats may be the pathogenesis of arterial disease (3) non-hypotensive dose oftelmisartan can reduce blood sugar, blood lipid disorders and to reduceintimal hyperplasia after vascular injury, probably by increasing localarterial intimal expression of ACE2play a vascular protective effect;(4)Lower expression level of ACE2in artery intima may one of themechanisms which incidence arterial disease in diabetic rats.(5)ARBmay play a role in vascular protection, partially through an increase inintima of ACE2expression.(6) Telmisartan group caused a significant increase in ACE2protein compare to fosinopril group，and both drugsgroup caused no significant increase in ACE2mRNA though threetherapied groups.