Effect Of Notoginsenoside Fc On Re-endothelialization In Peripheral Vascular Lesions Of Diabetic Rats

Objective: Diabetes could reduce the ability of vascular endothelial cell injury repair and delay the reendothelialization,resulting in a high rate of restenosis after interventional treatment of diabetic peripheral vascular disease.The purpose of this study is to investigate the effect and mechanism of a novel Chinese medicine monomer,notoginsenoside Fc,on the vascular endothelial cell dysfunction,re-endothelialization and intimal hyperplasia in diabetic rats.Methods: 1.Animal experiments: A total of 48 female Sprague-Dawley rats were randomly divided into four groups: sham operation group,control group,diabetes group,and Notoginsenoside Fc group.We established a rat model of type 2 diabetes by high fat feeding and small dose(40 mg /kg)STZ intraperitoneal injection,then followed by carotid balloon interventional injury in the successful model rats.The experimental group was administered by gavage Notoginsenoside Fc.We harvest the vascular tissue at 7 and 14 days after intervention,then the re-endothelialization of injured vessels was observed by Evan blue staining,the intimal hyperplasia was observed by HE staining and immunofluorescence staining.2.Cell experiments: Rat aortic endothelial cells(RAOECs)were cultured in vitro,and cells were stimulated with 30 mM glucose to cause a high glucose environment,and treated with 20 ?M notoginsenoside Fc.The proliferation,apoptosis and migration of RAOECs were detected by CCK-8,FITC/PI double staining kit,transwell chamber and so on.The autophagy was observed by electron microscopy and laser confocal techniques.The fluorescence quantitative PCR and Western blotting were used to detect mRNA and protein levels of some apoptosis and autophagy-related genes.Results: 1.With the increase of glucose concentration,the apoptosis of RAOECs increased,the proliferation and migration ability decreased,while notoginsenoside Fc could improve the dysfunction caused by high glucose on endothelial cells.2.High glucose reduced the expressions of LC3 B and Beclin1 in RAOECs,increased the expression of p62,decreased autophagosomes under electron microscope,and decreased the autophagic flow detected by immunofluorescence staining.In summary,the autophagy ability of RAOECs decreased under high glucose conditions,while Fc treatment can increase the autophagy of vascular endothelial cells.3.The re-endothelialization following carotid artery injury in diabetic rats was significantly delayed compared with normal rats,while Fc treatment group accelerated re-endothelialization in diabetic rats.4.The intimal hyperplasia was significantly serious in diabetic rats following carotid injury than in normal rats,while Fc treatment group inhibited intimal hyperplasia in diabetic rats.Conclusions: Notoginsenoside Fc can improve endothelial cell dysfunction,accelerate re-endothelialization and inhibit excessive intimal hyperplasia by increasing autophagy of vascular endothelial cells in high glucose conditions,thus play an important role on preventing the early restenosis after interventional therapy of diabetic peripheral vascular diseases.