Expression Of Jagged1、Notch1 After Aortic Endothelial Balloon Injury In Rats And The Eeffect Of Valsartan On It

Objective(1)To analyze the relationship between aortic endothelial injury and intimal thickening,expression of Jagged1 and Notch1 via observing the degree of neointimal thickening and the expression of Jagged1 and Notch1 in aortic tissue after aortic endothelial balloon injury in Rats.(2)The endothelia injury rats were treated with valsartan(20mg/Kg/d).We detect the levels of neointimal hyperplasia and expression of Jagged1 and Notch1,and analyse their relationship.(3)To explore the process of intimal thickening and vascular restenosis after aortic vascular endothelial injury via establishing animal models.(4)To Discuss the role of valsartan in preventing coronary restenosis and the potential mechanism after endothelial injury caused by percutaneous coronary intervention(PCI).Methods 64 healthy Wistar rats were randomly divided as operation group,sham operation group,sham treatment group and treatment group.The endothelial injury rat models whose endothelial were injured by self-made 2F balloon were made,to simulate the process of coronary endothelium injury after PCI.We simulate the process of postoperative treatment with valsartan by intervening rats with ARB.At the 14 days and 28 days after operation,the neointimal thickening was observed by hematoxylin-eosin(HE)staining,and the intima and media thickness were measured.Immunohistochemistry and Western blotting(WB)was used to detect the protein expression of Jagged1 and Notch1 in rat aortic tissues.The levels of Jagged1 and Notch1 m RNA in rat aortic tissues were detected by real-time quantitative reverse transcription polymerase chain reaction(q RT-PCR).The one-way analysis of variance was used to analyze the data,the relationship between the endothelial thickening and the change of Jagged1 、 Notch1 in aortic tissues was discussed,and the effects of valsartan on it were explored.Results(1)At the 14 and 28 days after the aortic balloon injury in rats,in operation group,the neointimal which was constructed by new endothelial layers,proliferated smooth muscle cells and deposited extracellular matrix,was significantly thicker than that in sham operation group(P<0.01).The middle layer of the operation group was thicker than that in sham operation group(P<0.05).There was no significant difference of the intimal thickness between the sham treatment group and the operation group(P>0.05).The intimal thickness in the treatment group was significantly reduced compared with the sham treatment and the operation group(P<0.01).(2)The levels of Jagged1 m RNA and protein in the aortic tissue of the operation group were significantly higher than that in the sham operation group at 14 and28 days after operation(P<0.01).The relative expression levels of Jagged1 m RNA and protein in treatment group were significantly lower than that in the sham treatment group(P<0.01).There was no significant difference in the relative expression levels of Jagged1 m RNA and protein between the treatment group and the operation group(P<0.05).(3)The expression levels of Notch1 m RNA and protein in the vascular tissue of the operation group was significantly lower than that in the sham operation group at 14 and 28 days after operation(P<0.01).The relative expression levels of Notch1 m RNA and protein in the treatment group were significantly higher than that in the sham treatment group(P<0.01).There was no significant difference in the relative expression levels of Notch1 m RNA and protein between the sham treatment group and the operation group(P>0.05).Conclusion(1)The migration and proliferation of vascular smooth muscle cells after aortic balloon injury lead to neointimal thickening;(2)The expression of Jagged1 was significantly increased and Notch1 decreased in the endothelial-injured aortic tissue;(3)After treatment with valsartan,the expression of Jagged1 was significantly decreased and the expression of Notch1 was significantly increased.(4)The proliferation of neointimal after aortic endothelial injury may be related to the up-regulated of Jagged1 and down-regulated of Notch1;(5)The effect of Valsartan inhibiting the neointimal thickening may be related with the inhibition of the migration and proliferation of vascular smooth muscle cells,down-regulation of Jagged1 and up-regulation of Notch1.