| Backgroud and object:Recent studies have shown: angiotensin- converting enzyme 2 (ACE2) is a protective factor in cardiovascular system, the production ACE2 decrease in diabetes vascular. Telmisartan is an unique angiotensin II receptor blocker(ARB) with selective PPARγ-modulating activity,it can improve insulin resistance and reduce the level of blood glucose.Statins have been used extensively for the treatment of diabetes macroangiopathy,but the combination of ARB and statins in the treatment of diabetic endothelial injury and its mechanisms is waiting for being illuminated. In this study, we treated diabetic rats by administration of single telmisartan, single atorvastatin and the combination of telmisartan and atorvastatin after carotid artery balloon injury, observed the effects on expression of ACE2 in the carotid artery intima after balloon catheter injury and the change of intimal hyperplasia after drug intervention preliminary investigate their potential mechanisms in preventing endothelial injury and to provid experimental proof for searching more effective treatment of diabetic macroangiopathy and resenosis after PTCA in clinical workMethods: Six of the 50 healthy male Sprague-Dawley rats were as randomly selected normal group(n=6),other 44 rats were used to establish model of diabetes. Six of the modeling diabetic rats were drawn out randomly as Diabetic control group and the others were randomly divided into 4 groups balloon injury alone group (balloon injury plus saline; n=6); telmisartan group (balloon injury+telmisartan 0.8mg/kg.d;n=7); atorvastatin group (balloon injury+atorvastatin 10mg/kg.d; n=6); and combination group (balloon injury+telmisartan 0.8mg/kg.d+atorvastatin 10mg/kg.d;n=7). All of the rats were examinated fasting blood glucose,blood lipids,insulin of tails blood and measured blood pressure, heart rate, body weight; 4 weeks after the drugs intervention,the target detection again; hematoxylin-eosin (Hematoxylin-eosin stain, HE) staining observation of carotid artery intimal hyperplasia, measured intima (intima, I) and the thickness of carotid (intima/Membrane, I/M) ratio. ACE2mRNA were measured by Reverse Transcriptase Polymerase Chain Reaction (RT-RCR). angiotensin-converting enzyme 2 (ACE2) protein expression of intimal were detected by Immunoblot (western blot, WB) .Results: (1) Compared with normal group:the systolic blood pressure (SBP) of diabetic group was no significant difference (P>0.05), blood lipids, serum insulin (FNS) was significantly increased(P<0.01); carotid artery intima-ACE2 mRNA and protein expression decreased significantly, respectively 0.38±0.10,0.521±0.03(vs nomal controlP<0.01)(2) Compared with diabetic group,the SBP of telmisartan group was no significant changes . SBP, blood glucose (FBG), FNS, blood lipids (TC, TG, LDL-c)in telmisartan group,atorvastatin group and combined intervention group were significantly lower (P<0.01);the thick of intima is significantly increased in balloon injury alone group,the ratio of the intima and medial (I/M) was significant difference (P<0.01); (3) compared with balloon injury alone, intimal hyperplasia in telmisartan and atorvastatin group reduce respectively is 0.122±0.019,0.125±0.018 (vs BI 0.202±0.006 P<0.01),ACE2 mRNA and protein expression was significantly increased (P<0.01); endometrium in combination group was significantly thinner,hyperplasia reduce, I/M were significantly different (P<0.01); (4)compared with telmisartan group,atorvastatin group,intimal hyperplasia in combination group is further reduced, ACE2 mRNA and protein expression were significantly different (P<0.01), but telmisartan group and atorvastatin group was no significant difference(P>0.05).Conclusions: (1) We can replicate the model of type 2 diabetes by feeding fat-rich and glucose-rich diet combined with intraperitoneal injection low dose STZ ;rat carotid artery balloon injury model which can stimulate diabetic macrovascular intimal hyperplasia is a ideal model to study the mechanism of neointimal formation and determine the anti-proliferative effect of drugs (2) intima decreased levels of ACE2 expression in diabetic rats may be the pathogenesis of arterial disease (3) non-hypotensive dose of telmisartan can reduce blood sugar, blood lipid disorders and to reduce intimal hyperplasia after vascular injury, probably by increasing local arterial intimal expression of ACE2 play a vascular protective effect; atorvastatin can reduce intimal hyperplasia to some extent (4) in the role of reducing intimal hyperplasia after balloon injury combined with Telmisartan and atorvastatin show more significant, suggesting that telmisartan combined with statins in prevention of diabetic vascular endothelial injury in synergy so as to clinical diabetes vascular injury and restenosis after PTCA provided the experimental basis for exploration.
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