| Objective Coronary artery bypass grafting vascular restenosis limits the overall effect of surgery; intimal hyperplasia after vascular endothelial injury is the central link of restenosis. AngⅡ is involved in cell growth regulation, and can lead to oxidative stress, inflammatory reaction and promote the formation of intimal hyperplasia. The newly discovered Ang-(1-7) may antagonize the effects of AngⅡ, resulting in the inhibition of intimal hyperplasia. This experiment aims to establish a rat model of autologous external jugular vein arterialization, simulate pathophysio logical process of vein graft after. The application of Ang-(1-7) and its specific receptor inhibitor A779, to investigate the effect of Ang-(1-7) on restenosis of autologous vein transplantation, and provide a theoretical basis for the clinical prevention of restenosis after reconstructive vascular operation.Methods 40 SPF male SD rats (weight 450-500g) were established, the external jugular vein to the abdominal aorta transplantation model,these mice were randomly divided into control group and blank gel group, Ang-(1-7) gel group, A779 gel group,10 rats in each group.Blank control group:saline spray only in the outer membrane of vein bridge;blank gel group:the vein bridge membrane evenly 20% Poloxamer 407 0.5ml;Ang-(1-7) gel group:the vein bridge membrane smear carrying angiotensin-(1-7) (10nmol/L) 20% poloxamer 407 0.5ml;A779 gel group:the vein bridge membrane smear carrying A779 (10nmol/L) 20% poloxamer 407 0.5ml.The four group respectively after 2W,4W each 5 rats were killed, the interception of vein grafts were fixed, embedded in paraffin, HE staining, and through computer image analysis determination of the variation in thickness of intima and media system, and calculate the ratio of I/M.The expression of PCNA、ERK、ATiR of graft vein was detected by immunohistochemistry.Results Each group of mice was no death due to surgery. At the fourth week, the lower extremity of a rat in group A which mobility is poor due to thrombosis. HE staining shows: Two time points after surgery (2W,4W), Ang-(1-7) group bridge vein intimal hyperplasia was significantly lower than that in blank control group and blank gel group, A779 group, the difference was statistically significant (P<0.05). Two time points after surgery (2W,4W), there was no difference between control group and blank gel group of endometrial hyperplasia (P>0.05). Two time points after surgery (2W,4W), there were differences between the control group and A779 group the degree of intimal hyperplasia (P<0.05). IHC shows:Two time points after surgery (2W,4W), the positive expression rate of PCNA、ERK、AT1R of Ang-(1-7) group’s bridge vein was lower than the blank control group and blank gel group, A779 group, the difference was statistically significant (P<0.05). Fourth weeks after surgery, there was significant difference in the expression of PCNA between blank control group and A779 group (P<0.05). Two time points after surgery (2W,4W), the difference in the expression of ERK、AT1R was significantly (P<0.05). Two time points after surgery (2W,4W), the positive expression rate of PCNA、ERK、AT1R between blank control group and blank gel group was no significantly difference.Conclusion Intimal hyperplasia is the main cause of restenosis after vein graft; intimal hyperplasia and mainly derived from vascular smooth muscle cells proliferation and migration. Ang-(1-7) expression can significantly antagonize AngⅡ receptor AT1R, inhibit the proliferation and migration of smooth muscle cells, reduce the role of AngⅡ in promoting intimal hyperplasia. Ang-(1-7) can inhibit the expression of ERK in vein grafts; both RAS and PKC-MAPK signal transduction system are involved in the vein graft intimal hyperplasia. |
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